Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8781

(v) Prevalence. The claim may percent or less of the DV for folate per being taken to help women of provide estimates, expressed on an serving or per unit. The example childbearing age to reduce their risk of annual basis, of the number of neural contains all required elements plus having a pregnancy affected with spina tube defect-affected births among live optional information: Women who bifida or other neural tube defects births in the United States. Current consume healthful diets with adequate (NTD’s) and to comply with the estimates are provided in § 101.79(b)(1), folate throughout their childbearing recommendation of the U.S. Public and are approximately 6 of 10,000 live years may reduce their risk of having a Health Service (PHS) that they consume births annually (i.e., about 2,500 cases child with a birth defect of the brain or at least 0.4 mg (400 µg) of folic acid among 4 million live births annually). spinal cord. Sources of folate include daily. This action also responds to a Data provided in § 101.79(b)(1) shall be fruits, vegetables, whole grain products, citizen petition submitted by Glenn used, unless more current estimates fortified cereals, and dietary Scott. from the U.S. Public Health Service are supplements. EFFECTIVE DATE: January 1, 1998. available, in which case the latter may (3) Example 4. Model health claim FOR FURTHER INFORMATION CONTACT: be cited. appropriate for foods intended for use Felicia B. Satchell, Center for Food (vi) Reduction in risk. An estimate of by the general population and Safety and Applied Nutrition (HFS– the reduction in the number of neural containing more than 100 percent of the 158), Food and Drug Administration, tube defect-affected births that might DV of folate per serving or per unit: 200 C St. SW., Washington, DC 20204, occur in the United States if all women Women who consume healthful diets 202–205–5099. consumed adequate folate throughout with adequate folate may reduce their SUPPLEMENTARY INFORMATION: their childbearing years may be risk of having a child with birth defects included in the claim. Information of the brain or spinal cord. Folate intake I. Background contained in paragraph (b)(3) of this should not exceed 250% of the DV Recent estimates state that there are section may be used. If such an estimate (1,000 mcg). (i.e., 50 percent) is provided, the approximately 4,000 pregnancies each estimate shall be accompanied by Dated: February 26, 1996. year, including 2,500 live births, that are additional information that states that David A. Kessler, affected by spina bifida and other neural the estimate is population-based and Commissioner of Food and Drugs. tube defects. In September 1992, PHS recommended that all women of that it does not reflect risk reduction Donna E. Shalala, that may be experienced by individual childbearing age in the United States Secretary of Health and Human Services. consume 0.4 mg (400 µg) of folic acid women. [FR Doc. 96–5013 Filed 2–29–96; 1:12 pm] (vii) Diets adequate in folate. The daily to reduce their risk of having a claim may identify diets adequate in BILLING CODE 4160±01±P pregnancy affected with spina bifida or folate by using phrases such as ‘‘Sources other NTD’s (Ref. 1). Furthermore, PHS of folate include fruits, vegetables, identified several possible approaches whole grain products, fortified cereals, DEPARTMENT OF HEALTH AND by which folate intake by the target and dietary supplements.’’ or ‘‘Adequate HUMAN SERVICES population could be increased. These approaches included: (1) Improvement amounts of folate can be obtained from Food and Drug Administration diets rich in fruits, dark green leafy of dietary habits, (2) fortification of the U.S. food supply, and (3) daily use of vegetables, legumes, whole grain 21 CFR Parts 136, 137, and 139 products, fortified cereals, or dietary folic acid supplements by women supplements.’’ or ‘‘Adequate amounts of [Docket No. 91N±100S] throughout their childbearing years. However, the PHS recommendation folate can be obtained from diets rich in RIN 0910±AA19 fruits, including citrus fruits and juices, cautioned against daily intakes of folate vegetables, including dark green leafy Food Standards: Amendment of above 1 mg. A recognized adverse effect vegetables, legumes, whole grain Standards of Identity For Enriched of high intakes of folate is a masking of products, including breads, rice, and Grain Products to Require Addition of the anemia of vitamin B12 deficiency, pasta, fortified cereals, or a dietary Folic Acid allowing the neurologic damage to supplement.’’ progress untreated. PHS noted that care (d) Model health claims. The AGENCY: Food and Drug Administration, should be taken to keep total folate following are examples of model health HHS. consumption at less than 1 mg (1,000 µ claims that may be used in food labeling ACTION: Final rule. g)/day, except under the supervision of to describe the relationship between a physician (Ref. 1). folate and neural tube defects: SUMMARY: The Food and Drug Following publication of the PHS (1) Examples 1 and 2. Model health Administration (FDA) is amending the recommendation, FDA convened a Folic claims appropriate for foods containing standards of identity for several Acid Subcommittee from its Food 100 percent or less of the DV for folate enriched grain products and, by cross- Advisory Committee (hereinafter per serving or per unit (general reference, the standards of identity for referred to as the Folic Acid population). The examples contain only enriched bromated flour, enriched Subcommittee) to consider some of the the required elements: vegetable macaroni, and enriched issues raised by the recommendation. (i) Healthful diets with adequate vegetable noodle products, to require After consideration debate, the Folic folate may reduce a woman’s risk of the addition of folic acid. The agency is Acid Subcommittee identified several having a child with a brain or spinal requiring that these products be fortified approaches that might assist women of cord birth defect. with folic acid at levels ranging from childbearing age to increase their daily (ii) Adequate folate in healthful diets 0.43 milligrams (mg) to 1.4 mg per folate intake. These approaches may reduce a woman’s risk of having a pound (mg/lb) or 95 micrograms (µg) to included: (1) Development of a child with a brain or spinal cord birth 309 µg/100 grams (g), of product. These fortification program such that 90 defect. values are based on a fortification level percent of women of childbearing age (2) Example 3. Model health claim of 140 µg/100 g (0.635 mg/lb) of the could receive at least 400 µg per day appropriate for foods containing 100 cereal grain product. This action is from all sources, while preventing 8782 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations excessively high folate intakes by increasing the possibility of Guide Pyramid, and consume cereal- nontarget groups; (2) appropriate uncontrolled fortification of the food grain products fortified with folic acid, labeling of foods, including dietary supply. Consequently, FDA said that to determine whether these consumers supplements; and (3) implementation of any fortification program that it adopted will have daily intakes in excess of the an educational program directed must be consistent with a safe range of recommended safe upper limit of 1 mg/ primarily at women of childbearing age intake for all population groups and yet day. that emphasizes the importance of folate be capable of maximizing the folate These estimates showed that intake before pregnancy, and continuing intakes of the target population within consumers who followed even the low- into early pregnancy and its potential this safe range. end of recommendations from the effect on reducing the incidence of The options that FDA considered for USDA Food Guide Pyramid could, NTD’s. (For a detailed discussion of the providing folic acid to women of without supplement use, easily issues and concerns raised by the Folic childbearing age through food consume 420 µg or more of folate per Acid Subcommittee please refer to the fortification included the addition of day from cereal-grain products fortified Health Claims proposed rule (58 FR folic acid to cereal-grain products, fruit with 70 µg/100 g. Further, such 23254 at 23256) and the final rule juices, and dairy products. In weighing consumers’ daily intake could triple if authorizing a health claim about the these options, FDA considered the such products were fortified with 350 µg relationship between folate and neural effects of the inclusion of folic acid in folic acid/100 g. tube defects (hereinafter referred to as breakfast cereals and in dietary As a result of its analysis of the claims final rule) published supplements. The agency’s decision to fortification of several cereal-grain, elsewhere in this issue of the Federal factor the amount of folic acid supplied dairy, and juice products, FDA Register.) by breakfast cereals and supplements in tentatively determined that fortification After considering the suggestions of its estimates of the effects of fortification should be limited to cereal-grain PHS and the Folic Acid Subcommittee, is fully discussed in the folic acid health products and not extended to dairy FDA tentatively concluded that claims proposal (58 FR 53254 at 53276). products and fruit juices. The agency development and implementation of a In determining the appropriate levels noted that intakes by very large fortification program for the addition of of fortification with folic acid, the segments of the general population folic acid to the food supply could be an agency used the U.S. Department of could reach several milligrams per day effective part of an overall plan to Agriculture’s (USDA’s) 1987 to 1988 if all of these foods were fortified with increase the folate intake of women of national food consumption data (Ref. 2) folic acid. childbearing age to assist them in to estimate the daily intake of folate for The agency also tentatively decided reducing their risk of having a NTD- the target population, as well as for the that the appropriate fortification level affected pregnancy. Food fortification, general population, with fortification at for cereal-grain products was 140 µg/100 as noted by the Folic Acid different levels for cereal-grain g. Based on the results of its analysis, Subcommittee and expert speakers who products, dairy products, and juices. FDA determined that fortification of testified before the Folic Acid The agency estimated the effects of cereal-grain products with 140 µg/100 g, Subcommittee, has the advantage of fortification using three values: 70, 140, along with fortification of ready-to-eat reaching a great number of women in and 350 µg of folic acid/100 g of cereal- breakfast cereals up to 100 µg/serving the target population before conception grain product. As discussed in the folic and dietary supplements up to 400 µg and during early pregnancy. It also has acid health claims proposal, the value of per unit or per serving, would provide the advantage of providing folic acid in 70 µg/100 g (0.317 µg/lb) is the amount increased intakes of folate for women in a continuous and passive manner and, recommended in 1974 by the Food and their childbearing years, while keeping thus, represents a potentially effective Nutrition Board, National Research daily intakes for the nontarget means for improving the folate nutriture Council, National Academy of Sciences, population within the recommended of women throughout their childbearing and would restore the folate lost in the safe upper limit of approximately 1 mg/ years. However, fortification must be milling of cereal-grain products (Ref. 3). day. The agency noted that even with controlled to ensure that daily intake of The value of 140 µg/100 g is twice that supplement use, 95th percentile intakes folate by the target population, as well amount, and 350 µg/100 g is five times by adults 51+ years of age could reach as by the general population, is no more that amount. 840 to 860 µg/day if these enriched than 1 mg. FDA’s analysis showed that when cereal-grain products are fortified with The issues raised by a fortification fortification included fruit juices and 140 µg/100 g. While the agency program were highlighted for the agency dairy products in addition to cereal- recognized that this level approached in the Federal Register of October 14, grain products, ready-to-eat breakfast the recommended safe upper limit and 1993 (58 FR 53254), in a document cereals, and dietary supplements, did not take into account likely entitled ‘‘Food Labeling: Health Claims intakes by consumers in some nontarget underreporting biases regarding food and Label Statements; Folate and Neural groups exceeded 1 mg/day even at the intakes and underestimation of folate Tube Defects,’’ (hereinafter referred to as lowest level of fortification. However, content of foods, it tentatively the folic acid health claims proposal) when fortification is limited to cereal- concluded that fortification of cereal- when it proposed to authorize a health grain products at levels of 70 µg/100 g grain products with 140 µg/100 g folic claim about the relationship between or 140 µg/100 g, estimates of daily acid was the most appropriate folate and the risk of neural tube birth intakes remained below 1 mg/100 g. At fortification level of the three levels defects on the labels or in the labeling fortification levels of 350 µg/100 g, FDA analyzed. of foods and dietary supplements. In the estimated the daily intake to reach In addition to estimating daily intakes folic acid health claims proposal (58 FR levels of 1,220 µg/day, which exceeds of folate at the levels cited above, FDA 53254 at 53270), FDA acknowledged the recommended safe upper limit. reviewed the existing food additive that authorizing a health claim on folate The agency also estimated the daily regulation § 172.345 (21 CFR 172.345) and NTD’s would create the likelihood intake of folate for consumers who governing the use of folic acid to that manufacturers would fortify their follow Federal government dietary determine whether the regulation was products with folic acid so that they guidance, such as the U.S. Dietary adequate to ensure that addition of folic could qualify to bear the claim, thereby Guidelines and the DHHS/USDA Food acid to foods would be consistent with Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8783 the fortification proposals discussed enriched noodle products (§ 139.155 (21 that the agency wait until additional above. As a result of its review, FDA CFR 139.155)) and, by cross-reference, studies have been completed that better recognized that the existing regulation the standards of identity for enriched define the minimum level of folate lacked the guidance necessary for bromated flour (§ 137.160 (21 CFR needed to be effective or that identify manufacturers to decide which foods 137.160)), enriched vegetable macaroni other alternatives that would be are appropriate for fortification, and the products (§ 139.135 (21 CFR 139.135)), effective in increasing the daily folate levels at which folic acid can be added. and enriched vegetable noodle products intake of the target population. More importantly, FDA realized that the (§ 139.165 (21 CFR 139.165)). While FDA recognizes that there is regulation would not have limited the FDA received approximately 170 some uncertainty in the literature as to addition of folic acid to enriched cereal- letters in response to its proposal to the optimal intake of folate required to grain products, breakfast cereals, and amend the standards of identity for reduce the risk of NTD’s, PHS, in dietary supplements. In fact, the enriched cereal-grain products to examining the data from the available regulation as written would have require folic acid fortification at 140 µg/ human studies, found the evidence permitted folic acid addition to virtually 100 g. Each letter contained one or more sufficiently consistent to make its any food. comments. The letters were from a wide recommendation that all women Thus, in the same issue of the Federal range of sources, including individual capable of becoming pregnant should Register that the agency proposed to members of FDA’s Folic Acid consume 400 µg folic acid daily. This authorize a health claim about the Subcommittee and Food Advisory target intake goal represents the best relationship of folate and NTD’s (58 FR Committee, Federal and State scientific judgment based on available 53254 at 53270), it published a proposal Government agencies, a foreign data. It has also been supported by the entitled ‘‘Food Additives Permitted for government, health care organizations, Folic Acid Subcommittee. Direct Addition to Food for Human academia, consumer organizations, Furthermore, PHS, the Folic Acid Consumption, Folic Acid (Folacin)’’ (58 medical professionals, consumers, Subcommittee, as well as other medical FR 53312) (hereinafter referred to as the industry, and industry trade experts, recommended food fortification food additives proposal) to amend the associations. Some comments supported as part of an overall program to improve food additive regulation to restrict the various provisions of the proposal. the folate intake of women of addition of folic acid to specific foods. Other comments suggested childbearing age. This recommendation In that document, FDA proposed, modifications, revisions, or revocations is based on the fact that 50 percent of among other things, to establish a of various provisions of the proposal. pregnancies are unplanned, and that a limitation on the addition of folic acid Some comments raised concerns that large segment of women in the target µ to breakfast cereals of 100 g folic acid were more germane to issues discussed group will not use folic acid per serving, to retain current limitations in the folic acid health claims and food supplements daily. Thus, a passive µ (i.e., 400 g/daily) on the use of folic additive proposals. These comments means of ensuring that these women acid in dietary supplements, and to were forwarded to the appropriate have adequate folate intake is important. permit the addition of folic acid to foods dockets for response. Some comments The comments that opposed as authorized by the standards of raised issues that were outside the scope fortification did not submit any data in identity. The agency tentatively of this rulemaking and will not be support of their position. Thus, the concluded that such action was addressed in this final rule. A summary agency has no basis to reject the necessary to establish safe conditions of of the relevant comments, the agency’s recommendations of PHS and the Folic Acid Subcommittee to develop a folate use for folic acid in the food supply and responses to the comments, and a fortification program to assist women of still assist the target population, women complete discussion of the agency’s childbearing age in consuming at least of childbearing age, to achieve the goal conclusions with respect to the recommended by PHS that they 400 µg/day. µ fortification of enriched cereal-grain Although the agency is aware that consume at least 400 g of folate per products follow. day. there are several ongoing studies on the Also, in the October 14, 1993, issue of II. Comments and Agency Response relationship between folate and NTD’s, the Federal Register, FDA published a it has not been persuaded by the A. Fortification proposal entitled ‘‘Food Standards: comments to wait until additional Amendment of the Standards of Identity 1. The majority of comments studies have been completed to for Enriched Grain Products to Require recognized the need to assist women of determine what minimum level of folate Addition of Folic Acid,’’ (58 FR 53305) childbearing age to increase their daily intake is likely to be effective. The (hereinafter referred to as the standards intake of folate to reduce their risk of an agency has confidence in the data that of identity proposal) to amend the NTD-affected pregnancy. Many of these suggest that at intake levels of 400 µg/ following standards of identity to comments agreed with the PHS’ and day, the incidence of NTD’s can be require the addition of folic acid at a Folic Acid Subcommittee’s reduced. Thus, the agency concludes fortification level of 140 µg/100 g: recommendations that fortification of that it would not be in the best interest enriched bread, rolls, and buns the food supply is an appropriate of women in the target group to wait (§ 136.115 (21 CFR 136.115)); enriched approach to achieve this goal. Several until these studies are completed and flour (§ 137.165 (21 CFR 137.165)); comments, however, opposed the use of reviewed before implementing a enriched self-rising flour (§ 137.185 (21 fortification as a mechanism to address program to assist them in increasing CFR 137.185)); enriched corn grits this need. Some of the comments their daily intake of folate. (§ 137.235 (21 CFR 137.235)); enriched opposed fortification because of The evidence that is available corn meals (§ 137.260 (21 CFR uncertainties in the efficacy data. These supports the position that the 137.260)); enriched farina (§ 137.305 (21 comments stated that the available data consumption of folate plays an CFR 137.305)); enriched rice (§ 137.350 do not indicate what minimum level of important role in reducing the risk of (21 CFR 137.350)); enriched macaroni folate is needed to effect a significant neural tube birth defects. Weighing this products (§ 139.115 (21 CFR 139.115)); reduction in NTD’s, and they argued evidence and recognizing that the enriched nonfat milk macaroni products that, therefore, the decision to fortify is majority of women in the target (§ 139.122 (21 CFR 139.122)); and premature. These comments suggested population do not consume the levels of 8784 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations folic acid recommended to reduce the agencies to establish policy initiatives supplements alone will be sufficient to risk of neural tube birth defects (Ref. 1), equivalent to those used by the food and reach the target population when folate the agency concludes that it is dietary supplement industries to market intake is critical (i.e., before and during appropriate to implement a fortification their products. the first 6 weeks of pregnancy). program at this time. The agency disagrees with these During the first 6 weeks of pregnancy Further, the agency is concerned that comments. The agency is providing for many women are not even aware that without the limitations that it is fortification with folic acid only in the they are pregnant and would likely not adopting in this final rule, and in the standards of identity for enriched be under the care of a physician. Thus, final rule entitled ‘‘Food Additives cereal-grain products. Unenriched as stated in several comments, there Permitted for Direct Addition to Food cereal-grain products without folic acid would be no reason to expect the many for Human Consumption; Folic Acid will continue to be available. women who do not normally take (Folacin)’’ (hereinafter referred to as the Consumers will be able to select foods supplements daily to be motivated to food additives final rule) which is made with the unenriched version of change this behavior. Therefore, published elsewhere in this issue of the the product if they wish to avoid folic supplement use cannot be relied on as Federal Register, to control the addition acid. Furthermore, the estimated daily the sole source for increasing dietary of folic acid to the food supply, the intakes that will result from the level of folate intake. As discussed above, the authorization of the health claim about fortification established in this final rule use of fortification of cereal-grain folate and NTD’s may encourage are well below the level of folic acid products has the advantage of providing overfortification of the U.S. food supply traditionally used to treat persons with folic acid in a continuous and passive and increase the risk of folate deficiency. Therapeutic dosages manner and, therefore, should be an overconsumption of folate. Because the of folic acid used for treatment of folate effective means for improving the folate current food additive regulation does deficiency are generally in the range of nutriture of women in their childbearing not limit or specify the types of foods 1 to 5 mg/day and are administered years. that can be fortified with folic acid, under the supervision of a physician. 3. A few comments opposed to approval of the claim, without any other Therefore, the comments that suggest fortification suggested that, as an action by the agency, could encourage that fortification of enriched cereal-grain alternative, FDA encourage women in manufacturers to fortify a variety of products is an attempt to medicate the the target group to increase their daily foods to qualify the food for a health U.S. population simply have no basis in folate intake by increasing consumption claim. Consequently, without proper fact. of foods that naturally contain high control over the types of foods that can Furthermore, the intakes that are levels of folate such as blackeye peas. be fortified with folic acid, likely to result from the level of While FDA finds merit in the overfortification could result. fortification established in this final rule comments’ suggestion to encourage The amendment to the standards of do not present a health concern to the women in the target group to increase identity for enriched cereal-grain general population, especially in their daily folate intake by increasing products to require the addition of folic conjunction with the provisions of the their consumption of foods naturally acid at specific levels will help to food additive final rule published high in folate, the agency is not ensure that the addition of folic acid to elsewhere in this issue of the Federal persuaded that such action makes food the food supply is done in a safe, Register. FDA has projected the total fortification unnecessary. The dietary rational, and reasonable manner because daily intake of folate that is likely to guidance suggested by the comment can it will limit the number of foods that result from the levels of fortification that be used in conjunction with food can be fortified and limit the level of FDA is requiring and determined that it fortification, as part of a program fortification. The levels of fortification is well within the safe upper limit of designed to help women in the target established in this final rule, coupled intake. Moreover, cereal-grain products group to increase their daily folate with the provisions governing addition have a long history of being vehicles for consumption. A health claim about the of folic acid to nonstandardized foods improving the nutrient intake of the relationship between folate and NTD’s established in the food additives final U.S. population. FDA requires the on a food that qualifies to bear the claim rule, will meet the goal of increasing addition of niacin, thiamin, and will contribute to such a program, folate intake among women of riboflavin in the standards of identity regardless of whether the food naturally childbearing age while keeping the daily for enriched cereal-grain products to qualifies to bear the claim or qualifies consumption of folate below the safe improve the daily intake of these on the basis of its fortification level. In upper limit of 1 mg/day. nutrients. Fortification of these products addition, foods that naturally contain 2. Comments that opposed was instrumental in reducing the folate and qualify to bear a health or fortification asserted that consumers prevalence of diseases related to nutrient content claim are likely to be believe that fortification as proposed insufficient intake of these vitamins. highlighted as a source of this nutrient. denies freedom of choice and control In response to the comments that Such claims will encourage women in over daily folate intake and is, therefore, suggested that FDA rely on the use of the target group to select these foods as viewed as an attempt to medicate dietary supplements to increase daily a part of their diet. people without obtaining informed folate intake, the agency notes that in Most significantly, however, given the consent. These comments further requiring the fortification of enriched value of adequate folate intake by asserted that fortification, as proposed, cereal-grain products, it is not women of childbearing age and given subjects them to the risk of discounting the use of dietary the value of a program that allows overconsumption. As an alternative, supplements to assist women in the women to obtain adequate folate by these comments suggested that the effort target group to increase their daily folate simply consuming such staples as bread to increase dietary folate intake in the intake. In fact, the agency included the and rolls, FDA sees no reason not to target population focus on the use of use of dietary supplements in its require fortification of such foods, even dietary supplements because the estimates to determine the appropriate though foods exist that are naturally amount of intake can be better level for fortification of enriched cereal- high in folate. controlled. They suggested that FDA grain products. However, the agency is 4. Some comments opposed to work with other public health service not confident that the use of dietary fortification opined that fortification Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8785 would not assure physicians and health While the agency acknowledges that it patterns of consumption of these foods. care professionals that their patients are considered taking a similar approach to In addition, enriched cereal-grain obtaining adequate amounts of folate increase the amount of iron provided by products have a long history of being from the food supply because the the diet when it proposed to double the successful vehicles for improving the bioavailability of folate in foods is 25 to amount of iron added to enriched nutriture of the U.S. population and for 75 percent depending on the food. cereal-grain products, the agency did reducing the risk of nutrient deficiency As discussed in the folic acid health not finalize that proposal because of diseases. Thus, the agency concludes claims proposal, FDA considered significant safety concerns regarding the that enriched cereal-grain products are several issues in developing its options risk of iron storage diseases. Rather, the an appropriate vehicle to increase daily for fortification. With respect to issues agency retained the existing level of iron folate intake among women of of bioavailability, FDA concluded that fortification for cereal-grain products. childbearing age. In fact, the estimates bioavailability cannot be meaningfully The agency does not have similar safety that FDA developed in evaluating factored into fortification scenarios concerns about the level of folic acid options for folic acid fortification because issues of bioavailability are very fortification that it is requiring in this demonstrate that the addition of folic complex, and no systematic data are final rule because it has concluded, acid to enriched cereal-grain products, available on many of the factors that based on a safety review (as fully coupled with the addition of this affect bioavailability. Consequently, the discussed in the food additives proposal nutrient to breakfast cereals and dietary estimates developed by FDA focused and final rule), that this required level supplements, will help to significantly more on consumption patterns of is safe and will not result in increase the daily folate intake of various staple foods, and their overconsumption of folate. women in the target group (see Table 7 of 58 FR 53254 at 53295)). availability and use in the U.S. food B. Covered Products supply, than on the bioavailability of Furthermore, increasing awareness of folic acid from a specific food. 7. Some comments stated that dietary the role of folate in reducing the risk of consumption studies indicate that The comment did not provide neural tube birth defects through the use women of reproductive age are less information to persuade the agency that of health claims and other educational likely than other groups to consume the complexity associated with initiatives should encourage women in enriched cereal-grain products that bioavailability would significantly the target group to increase their daily conform to a standard of identity, and reduce the effectiveness of food folate intake by consuming folate that, therefore, the use of such foods as fortification as part of an overall effort containing foods, including enriched a vehicle for folic acid fortification to improve folate nutriture among cereal-grain products. Consumption of would not significantly affect the risk of women in the target group. cereal-grain products is also likely to be NTD’s. These comments argued that, influenced by current dietary guidelines 5. Two comments recommended instead, fortifying these foods will only that promote increased consumption of revising the proposal to require the increase the amount of daily folate these foods. addition of vitamin B12 in a one-to-one intake among the nontarget groups. 8. Other comments requested that ratio with folic acid. The comments In selecting cereal-grain products as FDA permit the addition of folic acid to contended that doing so will not only vehicles for fortification, the agency other cereal-grain products such as prevent vitamin B12 deficiency, but it started with the basic principle that whole grain flours, breads, cereals, will also prevent the masking effect that fortification of staple products that are macaroni products, rice, and grits and may be caused with high consumption commonly consumed in significant not just the enriched cereal-grain foods of folate. One comment urged FDA to amounts by virtually all members of the that conform to a standard of identity. design research that will determine the target population is most likely to result The comments argued that without safety and effectiveness of fortifying the in increased intakes of a specific these products being fortified, food supply with vitamin B12 along with nutrient by the target population. consumers may be encouraged to eat folic acid because such fortification Although the agency recognizes that enriched refined grains instead of their could eliminate the adverse effect of current survey data suggest that whole grain counterparts and folate on vitamin B12 deficiency. consumption of enriched grain products consequently follow dietary patterns The agency is not persuaded that the may be somewhat lower in the target that are inconsistent with current approach suggested by these comments population than in other groups, these dietary guidelines to eat whole grain addresses all of the safety concerns foods still are reported to be consumed products. relating to persons with vitamin B12 on a daily basis by more than 90 percent FDA did not propose to provide for deficiencies. As fully discussed in the of women of childbearing age (Ref. 4). the addition of folic acid to whole grains food additives final rule, FDA rejects In addition, data show that the or products from whole grains because, this recommendation because the difference between target and nontarget traditionally, these products are not available data do not establish that populations in consumption of other enriched. Whole grain wheat products requiring the addition of vitamin B12 foods considered as fortification naturally contain higher levels of the B whenever folic acid is added will vehicles, such as dairy products and vitamins, including folate, because the eliminate the safety concerns relating to juices, is even greater (Ref. 4). Therefore, germ and bran layer are not removed persons with vitamin B12 deficiencies the other foods would be no more when the wheat kernel is processed. that arise because of deficiencies in appropriate as fortification vehicles for FDA’s standards of identity for cracked intrinsic factor (pernicious anemia) or maximizing folate intake by the target wheat, crushed wheat, and whole wheat other B12-related deficiencies. group, and yet maintaining safe flour, in §§ 137.190, 137.195, and 6. Two comments opposed to consumption by nontarget groups, than 137.200, respectively, state that the fortification stated that FDA should take cereal-grain products. proportions of the natural constituents the same position with respect to folic The agency notes that cereal-grain of such wheat, other than the moisture, acid fortification that it did when it products were recommended by the remain unaltered by the manufacturing decided not to fortify foods with iron in Food and Nutrition Board in its 1974 process. In establishing the standards of the 1970’s because of the concern about report on food fortification as identity for the enriched cereal-grain iron storage diseases. fortification vehicles because of the products, the agency’s initial goal was to 8786 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations restore thiamin, niacin, and riboflavin, appropriate option was to limit level of folic acid recommended to nutrients that are removed when the fortification to enriched cereal-grain reduce the risk of having a neural tube bran layer and germ are removed during products. Aside from the fact that these defect affected pregnancy. the processing of wheat. Subsequently, products have a long history of The agency agrees with the latter the agency required the addition of iron successful use as vehicles for increasing comments. As discussed in the folic to the enriched grain and also provided nutrient intake among U.S. consumers, acid health claims proposal (58 FR for the optional addition of other consumption data and other relevant 53254 at 53279), fortification of cereal- nutrients, such as calcium and vitamin information reviewed by the agency grain products at 140 µg/100 g will D. show that these products are consumed produce a significant increase in daily The estimates that the agency has routinely on a daily basis by 90 percent folate intake, even for women who make relied on in selecting a fortification level of women in the target group. food choices from the ‘‘low’’ range of of 140 µg/100 g considered only Furthermore, some comments submitted the USDA Food Guide Pyramid and fortification of breakfast cereals, dietary to the docket by representatives of the consume only 5 servings/day of cereal- supplements, and standardized cereal grains industry stated that, grain products and 1 bowl of cereal enriched cereal grain products and did generally, these products can be easily containing a minimum of 100 µg of folic not include fortification of other fortified with folic acid. Therefore, FDA acid. From these sources alone, these nonstandardized or unenriched concludes that the enriched cereal-grain women will consume about 320 µg of standardized cereal-grain products. products are the appropriate foods for folic acid. Addition of a serving or two Consequently, including such foods in fortification, and that fortification of of vegetables, or of a serving of fruit, the fortification program could result in these products is not unfair to the will provide them with a folate intake a daily intake of folate that is above the industry. above 500 µg/day. Thus, fortification of safe upper limit of 1 mg/day. Thus, the cereal-grain products at 140 µg/100 g is agency is not persuaded by the C. Fortification Level an important step in assisting women of comment that other cereal-grain 10. In the standards of identity childbearing age achieve the PHS products should be fortified with folic proposal, FDA requested comments on recommendation of consuming 400 µg. acid. whether the proposed fortification However, if cereal-grain products With regard to the concern raised in levels discussed for enriched cereal- were fortified at 350 µg/100 g, and the the comment that fortification of grain products were appropriate. dietary choices indicated above were enriched cereal grain products may Comments responding to this issue were made, a ‘‘low’’ consumer would obtain encourage consumers to choose these varied. Some comments that supported 610 µg folic acid daily from these products over their whole grain fortification of cereal-grain products sources alone. Thus, at a fortification counterparts, the comment did not stated that the proposed levels were too level of 350 µg/100 g a ‘‘high’’ consumer provide any support for its concern. The low to have any appreciable effect on could reach intakes of folic acid of more decision to fortify enriched cereal grain reducing the risk of NTD’s in the target than 1 mg/day from bread, noodle, rice, products at the level of 140 µg/100 g is population. One of these comments and pasta products alone. Additional based on current dietary consumption urged the agency to revise its proposal consumption of breakfast cereals, fruits, patterns. The agency is not persuaded and require fortification at levels of at vegetables, and a dietary supplement by by the comments that the addition of least 210 µg/100 g. However, the ‘‘high’’ consumers could result in daily folic acid will significantly change majority of these comments intakes of folate of about 2.5 mg/day, a consumption patterns of the target recommended that FDA require level significantly above the safe upper population. There is no evidence that fortification of folic acid within the limit of daily intake of 1 mg. women will suddenly start consuming range of 250 to 350 µg/100 g. In support The comments supporting enriched products instead of whole of their position, these comments fortification of enriched cereal-grain grain foods. In fact, one reason the contended that this range was well products at levels above 140 µg/100 g agency has decided to require the within limits for safety and should not did not provide any information to the fortification of enriched cereal-grain mask the effects of vitamin B12 agency that it had not considered in products is to enable women of deficiency. One comment further argued developing its proposed rules. Nor did childbearing age to significantly that at a fortification level of 350 µg/100 the comments offer alternative increase their daily folate intake without g, 95 percent of persons in the nontarget fortification schemes that would allow changing their dietary habits. Finally, population would not consume more addition of folic acid to enriched cereal- the agency notes that while current than 1 mg per day. One comment grain products at levels exceeding 140 dietary recommendations do encourage recommended 400 µg/100 g for cereal- µg/100 g yet limit the daily intake of increased consumption of whole grain grain products. This comment argued folate to levels that are within the safe foods, they also encourage consumption that fortification of enriched cereal-grain upper limit of 1 mg/day. Consequently, of all cereal-grain products. products should be at the same level as FDA disagrees with those comments 9. One comment expressed concern dietary supplements. that suggested that enriched cereal-grain that the agency’s tentative decision to However, supplemental comments products be fortified at levels of at least fortify cereal-grain products was unfair submitted by a majority of the 210 µg/100 g. There simply is no to the cereal-grain industry because it organizations supporting a higher evidence in the record that such a singled out one segment of industry to fortification level, stated that fortification program would keep folate address a health concern. (The agency implementing fortification at a level of intakes within the safe upper limit. notes that the comment was not at least 140 µg/100 g will constitute a Accordingly, as proposed, the agency submitted by a member of the cereal critically important step forward for the is requiring the addition of folic acid to grains industry.) health of American children. Some of enriched cereal grain products at a As discussed in the folic acid health these comments further stated that fortification level of 140 µg/100 g. FDA claims proposal, FDA considered fortification with at least 140 µg/100 g concludes that 140 µg/100 g is the several options that included will be the most efficient and cost- maximum level of fortification of fortification of dairy products and juices effective approach to ensuring that enriched cereal-grain products that before concluding that the most women of childbearing age consume the would be safe for all groups. Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8787

Nonetheless, as the agency states in the PHS recommended levels of 400 µg/ However, the majority of the comments the final rule on the use of folic acid as day without changes in their food that responded to this issue stated that a food additive, which is published selection practices (see Table 4 of 58 FR fortification should be voluntary. The elsewhere in this issue of the Federal 53254 at 53292). While the agency must comments cited varied reasons in Register, given the nature of the support ensure that the use of folic acid in the support of their position. Some for higher folic acid fortification levels food supply is safe, it must also provide comments stated that the addition of in the comments, if evidence becomes as great an opportunity as is prudent folic acid to enriched cereal-grain available to support that there is a and rational for all women of products should be optional pending reasonable certainty of no harm at folate childbearing age to increase their intake further evidence that the benefits intakes above 1 mg/day, FDA would be to the recommended level. The agency outweigh the risk of masking vitamin willing to reconsider the fortification concludes that a level of 140 µg/100 g B12 deficiency. These comments levels that it is adopting and to consider is the most appropriate fortification contended that mandatory fortification raising those levels. level for enriched cereal-grain products of a wide variety of common products 11. Other comments opposed because, based on the results of its may create difficulty for people wishing fortification at the proposed level of 140 estimated daily intakes, fortification at to avoid folic acid. Furthermore, the µg/100 g on the grounds that it is too this level will provide daily intakes for comments asserted that FDA failed to high. These comments asserted that the nontarget population that remain establish why mandatory fortification such fortification may increase the risk within the recommended safe upper would be necessary given that under of consuming folate at levels in excess limit of 1 mg/day, while providing current regulations voluntary of the safe upper limit of 1 mg/day in increased intakes of folate for women in fortification of standardized foods with a substantial portion of the general their childbearing years (see Table 7 of folic acid is prohibited. population. Some of these comments 58 FR 53254 at 53295). Other comments recommended suggested that FDA consider the lower The agency notes, however, that it has optional fortification so that millers will fortification level of 70 µg/100 g in reconsidered its proposed fortification not have to change their enrichment conjunction with an educational level for breakfast cereals. As fully premixes for the general flour supply, campaign that could still be effective in discussed in the food additives final thereby minimizing the costs associated reducing the risk of NTD’s yet not pose rule, published elsewhere in this issue with fortification, i.e., label changes, the risk of daily consumption of folate of the Federal Register, FDA is analytical testing, and inventory and in excess of 1 mg/day. permitting breakfast cereals to contain supply coordination, especially for In support of their position, some of up to 400 µg of folic acid per serving. products exported to countries that do these comments noted that the Food and As explained in that document, the not permit folic acid fortification. The Nutrition Board recommended the estimates for total daily folate intake comments also stated that voluntary fortification of cereal-grain products at that FDA presented in the folic acid fortification would facilitate compliance 70 µg/100 g to restore folate lost in the health claims proposal were based on with the various State enrichment laws. milling of cereal-grain products. the assumption that all breakfast cereals A few comments opposed to Another comment supporting were fortified at 400 µg/serving. Based mandatory fortification stated that FDA fortification at the restoration level on those estimates, daily folate intake failed to offer information as to why contended that such action would for certain groups in the nontarget voluntary fortification would not be permit additional restorations of population could exceed the sufficient to accomplish the public nonstandardized foods such as breakfast recommended safe upper limit of 1 mg/ health goal of decreasing the incidence cereals. One comment from a foreign day. Currently, however, only about 3 to of pregnancies with neural tube birth government questioned FDA’s decision 6 percent of breakfast cereals fortify at defects. The comments urged FDA to to require folic acid fortification of all 400 µg/serving. The agency has found establish a voluntary fortification enriched cereal-grain products when the no reason to expect that this percentage program for enriched cereal-grain data do not clearly establish the will change and, therefore, considers it products and to reassess the need for a effectiveness and safety of the proposed unlikely that daily folate intake in the mandatory fortification in several years. intervention program. However, the nontarget population will exceed 1 mg One of these comments acknowledged, comment suggested support of the Food with the fortification program adopted however, that it is difficult to predict and Nutrition Board’s 1974 proposal for in this final rule and in the food the extent of voluntary fortification. cereal grain fortification, i.e., additives final rule. A small number of comments fortification with folic acid at 70 µg/100 supported voluntary fortification for g. D. Optional Versus Mandatory only the enriched noodle and macaroni In the standards of identity proposal, Because of the increased health risk to products. The comments contended that FDA tentatively concluded that persons with vitamin B 12 deficiency voluntary compliance is consistent with fortification of cereal-grain products caused by increased levels of folate FDA’s current standards of identity for with 140 µg/100 g folic acid was the intake, FDA solicited comments in the enriched noodle and macaroni products most appropriate fortification level of standards of identity proposal on with regard to vitamin D, calcium, and the three levels analyzed to ensure that whether the addition of folic acid to wheat germ. folate intakes by the target population enriched cereal-grain products should The agency does not agree with the would increase. The comments have not be required as proposed or made comments that argued that the persuaded the agency that a fortification optional. fortification of enriched cereal-grain level of 70 µg/100 g could be as effective 12. A few comments fully supported products should be voluntary. In in assisting women in the target the agency’s proposal to require folic accepting the PHS’ and Folic Acid population to achieve the PHS acid addition to the enriched cereal- Subcommittee’s recommendation to recommended daily intake of 400 µg. In grain products. These comments include fortification as part of an overall fact, at a fortification level of 70 µg/100 contended that required addition of plan to increase the folate nutriture of g, the estimated daily folate intake by folic acid was an appropriate means of women of childbearing age, FDA has ‘‘low’’ consumers among women of increasing the daily folate intake of concluded that in order for a childbearing age is not likely to reach women in the target population. fortification program to be effective, 8788 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations

fortification must be mandatory for the that a daily intake of up to 1 mg of folate for persons affected with vitamin B12 enriched cereal-grain products. FDA is is safe. deficiency or any folate-related diseases, concerned that if it made fortification In response to concerns raised by then FDA should increase the voluntary, and voluntary fortification millers regarding label changes, fortification levels in grain products or were not widespread, there would be analytical testing, and inventory and other foods and require that upper safe only a negligible increase in the daily supply coordination, FDA recognizes limits be disclosed in higher dose folate intake of the target group, and the that manufacturers will need ample products. This comment urged FDA to intent of this rulemaking would have time to implement the changes required initiate a rulemaking to restore refined been defeated. FDA finds that there is a by this amendment of the standards of grain products with most of the public health need for women in their identity. As discussed below in the vitamins and minerals that are removed childbearing years to have adequate effective date section, FDA is permitting during milling as recommended by the folate intake, and that the only way that manufacturers time to coordinate any Food and Nutrition Board in 1974. The it can ensure that they will have such necessary changes that need to be made comment stated its belief that such an an intake is through mandatory throughout the chain of food production approach would raise few safety fortification. to comply with the requirements concerns and would not be costly FDA has traditionally used mandatory established in this final rule as well as because manufacturers are already fortification to restore nutrients lost with the requirements set out in part equipped to add nutrients to food. during the processing of cereal grains 101 (21 CFR part 101). FDA cannot at this time commit to and thereby to address the need for The agency notes that manufacturers increasing the levels of folic acid that reducing the risk of certain vitamin will continue to have the option of may be added to food within the next deficiency-related problems. The using unenriched cereal-grain products several years. However, as stated above, comments have not persuaded the as ingredients in foods and to add should data become available that enrichment nutrients to those products agency that the same basic approach demonstrate that modifications need to as they choose. Several comments from should not be applied in this case, be made to improve the effectiveness of industry representatives raised a where low folate intake represents a risk the intervention program, and evidence concern that the provisions in the food factor for a neural tube defect-affected be developed that the safe upper limit additive proposal would not permit pregnancy. USDA consumption data can be raised, FDA will decide what addition of folic acid at the bakery site. show that 90 percent of women of action is necessary. The agency notes, To the contrary, as discussed in the food childbearing age consume cereal-grain however, that the action it is taking in additives final rule, FDA will permit this rulemaking will more than products. Thus, mandatory fortification addition of folic acid at the bakery site compensate for the amount of folate lost of cereal grains will, as stated above, as long as it is in compliance with the during the milling process. increase folate intake among the target governing standard of identity. As for the comment’s request that group, without requiring significant Consequently, manufacturers will have FDA initiate rulemaking to restore to change in dietary patterns. the same option of adding folic acid as refined grain products other vitamins Consequently, mandatory fortification of they have with other enrichment and minerals that are removed during enriched cereal grains will help to nutrients when preparing foods that are milling raises, the agency notes that the ensure that the daily intake among the made with unenriched cereal-grain request issues outside the scope of this target group will reach the PHS µ ingredients. The agency notes, however, rulemaking. Therefore, no action on this recommended level of 400 g. Voluntary that any products marketed as a request is appropriate at this time. fortification does not offer the same standardized enriched cereal-grain 14. Several comments raised concern likelihood that folate intake will result product will have to contain folic acid regarding the impact of the proposed in intakes that approach the PHS at the levels established in this final regulation on foreign trade. One recommendation because the decision rule, and that these requirements comment from a foreign trade to fortify with folic acid will be at the preempt state enrichment requirements association urged FDA to delay discretion of individual manufacturers. that are not identical (see section 403(a) finalizing the proposed regulation to Therefore, voluntary fortification will of the act (21 U.S.C. 343(a))). provide the International Harmonization not adequately address the need for With regard to exported products, the Working Groups the opportunity to increased folate intake among women of agency recognizes that manufacturers review the proposal and recommend a childbearing age. may be required to maintain separate strategy that would serve public health FDA derived the fortification levels inventories for foreign and domestic goals, while achieving the spirit and established in this final rule based in sales. While FDA recognizes the intent of the North American Free Trade part on a safe upper limit of 1 mg folate/ importance of reducing trade barriers, Agreement (NAFTA). Another comment day. The agency has concluded that its first obligation is to protect and stated that the extra costs and inherent mandatory fortification of the enriched promote the health of U.S. consumers. inefficiencies of separate production cereal-grain products at the levels In that regard, the agency concludes runs could preclude some provided in this final rule is not likely that, because the fortification program manufacturers from the export to increase the risk of ‘‘masking’’ anemia adopted in this final rule is necessary to marketplace. in vitamin B12 deficient persons. Thus, significantly reduce the incidence of Other comments stated that the lack the fortification program that FDA is neural tube defect affected pregnancies, of consistent requirements for folic acid adopting will help to ensure that the it would not constitute an illegal trade fortification between major trading amount of folate that people in all barrier. partners, e.g., the United States and groups of the population can reasonably Canada, would create problems in cross- be expected to consume will not exceed E. Other Issues border trade and could result in higher 1 mg/day. As discussed in the food 13. One comment from a consumer costs for both U.S. and foreign additives final rule, the agency has interest group recommended that if consumers. Furthermore, these examined the available data on the research and monitoring does not comments asserted that inconsistent levels of folate that may mask anemia of establish in the next 2 years that the risk requirements could reduce the vitamin B12 deficiency and concluded of increasing folate intakes is significant competitiveness of domestic Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8789 manufacturers who export their level of folic acid used in the or rice, or for preparations (e.g., products. Thus, the comments urged production of all enriched cereal-grain semolina or other ingredients) used for FDA to resolve the issue of exporting products. Providing for a single level, manufacturing enriched macaroni or folic acid enriched products to foreign with provision for reasonable overages noodle products. The nutrients, which countries by working with foreign within the limits of current good usually are in the form of a fine powder, governments to permit export of folic manufacturing practice (CGMP), has have a tendency to settle out and to acid-enriched food. worked well with the other nutrients make uniform blends with the cereal FDA recognizes that the provisions it (thiamin, niacin, riboflavin, and iron) grains more difficult to achieve. In such is adopting in this final rule may be required to be added to enrich bread, instances, manufacturers, depending on inconsistent with the fortification rolls, and buns and various flour their application process, may select policies of other countries. However, as products. The provision for ‘‘reasonable target levels at the upper end of the discussed above, the agency finds that overages’’ in the standards for enriched range to ensure that the minimum levels the action that it is taking in this final bread, rolls, and buns (§ 136.115(a)(3)) established for the nutrients will be met. rule is necessary to adequately protect and enriched flour (§ 137.165(c)) Thus, to enable manufacturers to adhere the public health of U.S. consumers. provides manufacturers with flexibility to procedures that will deliver the FDA will continue to work with officials to ensure that required levels for the minimum level of nutrients required by in other countries, particularly parties to added nutrients will be met, and that the standards and to compensate for NAFTA, to find ways to reduce barriers these levels will be maintained variables in the processing operations, to cross-border trading of cereal-grain throughout the shelf life of the food the agency is continuing to provide for products and other foods. under customary conditions of nutrient additions in terms of ranges for F. Specific Standards of Identity distribution and storage. While FDA is the other enriched foods as set forth not establishing a specific upper limit below. In this document, the agency is for folic acid addition, the agency FDA also notes that the regulations for providing for the addition of folic acid advises that reasonable variations for nutrition labeling in § 101.9(g)(4)(i) µ at the level of 140 g/100 g to the overages of folic acid will be assessed require that added nutrients be present individual enriched cereal-grain on the same basis as that for the other in the food at levels that are at least products that are the subject of added nutrients in these foods. Those equal to the amount declared on the standards of identity. The agency reasonable variations are based on a label. In addition, § 101.9(g)(6) provides described indepth the method that it number of factors, including the for reasonable overages within the limits used in arriving at the levels of addition technology of nutrient addition, the of CGMP. Thus, the manufacturer bears for folic acid in the specific standards of possibility of nutrient deterioration, the the responsibility of ensuring that not identity in the standards of identity firms’ quality control procedures, and only will the requirements for added proposal. FDA will not describe that appreciation by the manufacturer of nutrients in the respective standards of method again in this document except these factors. identity be met, but also that the content to the extent that clarification is FDA acknowledges that some of the of any added nutrient is accurately warranted in response to specific standards for enriched cereal-grain declared in nutrition labeling. comments. For a complete discussion of products that are the subject of this final Therefore, consumers should receive the the basis on which FDA established the rule specify the levels of added nutrient stated quantity of each added nutrient enrichment levels for the subject (thiamin, riboflavin, and iron) in terms whether the standard provides for the standards of identity, the agency refers of ranges, and FDA has continued this added nutrient in terms of a single level interested persons to the standards of approach with respect to the addition of or a range. identity proposal (58 FR 53305 at 53307 folic acid in those products. In addition, a. Enriched flour. No specific to 53309). the agency notes that it received a comments were received on the petition (Docket No. 94P–0413/CP 1) fortification of enriched flour with folic 1. Bakery and Wheat Flour Products subsequent to the issuance of the folic acid. Thus, as proposed, FDA is 15. One comment, while supportive of acid health claims proposal to amend requiring that enriched flour contain 0.7 the proposal to fortify cereal-grain the standards for enriched macaroni and mg/lb of folic acid. FDA derived this products, suggested that a range of noodle products to provide for nutrient value by adding the fortification level of levels be permitted for addition of folic addition in terms of a single level with 0.635 mg/lb to the Food and Nutrition acid to all enriched cereal-grain provision for reasonable overages. Board’s folate value of unfortified flour products because of the inherent However, FDA is not making the change of 0.076 mg/lb, which yields 0.711 mg/ variation in the addition of the vitamins, to a single enrichment level in those lb. The agency rounded this value to 0.7 the distribution of the vitamins in a standards at this time because, while it mg/lb. Accordingly, based on this food, and the analytical methodology. has reached a final decision on folic calculation, FDA is amending the The comment suggested that FDA acid fortification, it has not had an standards of identity for enriched flour permit the addition of folic acid within opportunity to fully analyze the (§ 137.165) and enriched self-rising flour a range of 24 to 35 percent over the petition. FDA is not aware of any reason (§ 137.185), and, by cross-reference, amount established for each individual why it should delay action in the enriched bromated flour (§ 137.160), to standard. For example, the comment present rulemaking while it analyzes the require that these foods contain 0.7 mg/ suggested that the proposed amount of petition. Thus, until such time as the lb of folic acid. 0.7 mg/lb for enriched flour should be agency rules on the petition, the b. Enriched bread, rolls, and buns. revised to 0.7 to 0.91 mg/lb. The standards in question will continue to FDA is amending the standards of comment argued that this scheme is the provide for nutrient addition in terms of identity for enriched bread, rolls, and same as that used for enrichment in the ranges. buns in § 136.115 to require that these macaroni and noodle standards and is The ranges established in those foods contain 0.43 mg/lb of folic acid. needed for the same reasons that it is standards provide a measure of This rate of fortification is provided for in those standards. flexibility in selecting the target level proportionally consistent with the FDA does not agree that it is when nutrients are added to foods that fortification rate for the B vitamins necessary to provide for a range in the consist of large particles such as farina (thiamin, riboflavin, and niacin) when 8790 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations enriched flour is used in making these of the products because these uses are 2. Corn and Rice Products foods. For example, the levels of governed by other regulations. For thiamin, riboflavin, and niacin in example, when farina is used as an a. Enriched corn grits. No specific enriched flour (§ 137.165) are 2.9, 1.8, ingredient in the manufacture of comments were received regarding the and 24.0 mg/lb, respectively, and in precooked or instant breakfast cereal addition of folic acid to enriched corn enriched bread (§ 136.115) are 1.8, 1.1, products, the level of enrichment is grits. Thus, as proposed, FDA is and 15.0 mg/lb, resulting in a ratio of governed by the food additive regulation amending § 137.235 to require approximately 1.62 to 1. In the case of in § 172.345. That regulation provides fortification of enriched corn grits with the level of folic acid, the level for that such ready-to-eat cereals may be the same level of folic acid as that enriched flour is 0.7 mg/lb compared to enriched with folic acid up to 100 established for enriched wheat flour 0.43 mg/lb for bread, resulting in a ratio percent of the daily value per serving products, such that each pound of the 1.63 to 1. The levels of enrichment (i.e., 400 µg/serving). Neither this final food would contain at least 0.7 mg of specified for the B vitamins and folic rule nor the food additive final rule folic acid. FDA is also establishing the acid content are slightly lower in published elsewhere in this issue of the proposed upper limit for folic acid enriched bread products than in Federal Register, would affect the fortification of 1.0 mg/lb, which is enriched flour to allow the bread continued addition of folic acid to the approximately 50 percent higher than products to be made from the precooked or ready-to-eat breakfast the minimum of 0.7 mg/lb, as it has standardized enriched flour without cereals that are manufactured with done for the other B vitamins (thiamin, further fortification. farina. riboflavin, and niacin) that are required c. Enriched farina. In the standards of With respect to pasta products, the to be present in enriched corn grits. identity proposal, FDA proposed to agency notes that the standard of The agency notes that it published a establish a fortification level for folic identity for enriched macaroni and proposed rule in the Federal Register of acid in enriched farina (§ 137.305) on noodle products provides for the use of October 13, 1995 (60 FR 53480), that the same basis as that for enriched farina as an ingredient. However, the would revoke the standard of identity wheat flour, i.e., 1 lb of the food would agency is not persuaded that it should for enriched corn grits. If comments to contain not less than 0.7 mg of folic adjust the fortification level for farina the proposal support revocation of this acid. based on this possible use of this food. standard of identity, the provisions set One comment disagreed with the In cases where farina is used as an forth in this final rule for enriched corn agency’s rationale and argued that ingredient in an enriched macaroni or grits will also be revoked. FDA believes, enriched farina is a different product noodle product, the manufacturer has however, that enriched corn grits is a than enriched wheat flour and therefore the option of adding enrichment widely consumed food that is likely to should not be fortified at the same level nutrients to the farina at the flour mill be eaten by women in need of as enriched wheat flour. The comment or at the manufacturing facility to meet additional sources of folate. Therefore, asserted that farina is used differently the requirements of the standard of should FDA revoke this standard of than flour. For example, according to identity for enriched macaroni or identity, the agency is prepared to the comment, farina is often used as an amend § 172.345, the food additive ingredient in the less expensive pastas noodle products. One comment pointed out that farina regulation on folic acid, to include to replace the more expensive semolina. fortified grits to the list of The comment pointed out that farina is is not washed before cooking as had nonstandardized foods to which folic also eaten as a hot cereal, and that been noted in the proposal, and, thus, acid may be added. precooked breakfast cereals are fortified washing should not be a factor in with folic acid. The comment did not determining appropriate fortification b. Enriched corn meals. No specific offer an alternative fortification level or levels. comments were received regarding the data on which an alternative level could The agency acknowledges that current enrichment of corn meal products with be based. farina product labels do not suggest that folic acid. Thus, as proposed, FDA is Because both wheat flour and farina enriched farina products need to be amending the standard of identity in are made from the endosperm of wheat, rinsed before cooking. Thus, with § 137.260 to provide for a minimum that portion of the wheat kernel that current technology, rinsing of the folic acid level that is consistent with remains after the bran layer and germ enriched farina product would not be a that established for enriched flour, such have been removed, and because it is factor in deciding on an appropriate that each pound of the food contains 0.7 the bran layer and germ that contain value for vitamin and mineral addition mg. Because corn meal products may be most of the B vitamins, including the to farina. However, the agency notes used as substitutes for wheat flour naturally occurring folate, the amount of that the proposed upper limit was not products, the agency believes, as B vitamins lost during processing would based solely on the fact that the product discussed in the standards of identity be similar in both foods. Therefore, the may be rinsed but also on the fact that proposal (58 FR 53305 at 53308), that agency finds that it is reasonable to it may be diluted when prepared in consumers expect to be able to obtain fortify both flour and farina on the same other recipes. The comment did not the same levels of nutrients from basic level of 140 µg/100 g. offer data to persuade the agency to enriched corn meals as from enriched However, FDA acknowledges that deviate from the proposed upper limit wheat flour. FDA is also establishing an enriched farina and enriched flour may of folic acid addition. Thus, as upper limit for folic acid addition (i.e., serve different functions. Farina is often proposed, the agency is amending the 1.0 mg/lb which is approximately 50 used as a substitute for a flour- standard of identity for enriched farina percent higher than the minimum containing food, e.g., as a hot cereal at to provide for an upper limit for folic fortification level), as has been done for breakfast, with or without other cereal- acid addition (0.87 mg/lb) that is the added B vitamins. The upper limit grain products being consumed at that approximately 25 percent higher than on the other B vitamins is intended to meal, and it may be used in other foods the minimum of 0.7 mg/lb as it has done prohibit addition of excessive amounts such as pasta. However, the agency for the other B vitamins (thiamin, of the nutrient and to ensure uniformity finds no basis to change the fortification riboflavin, and niacin) that are required in composition of corn meals. FDA finds level based on these possible end uses to be present in enriched farina. that, for the same reasons, an upper Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8791 limit on the addition of folic acid of 1.0 demonstrates that addition of folic acid must be labeled with directions for mg/lb is necessary. to rice will result in off colors, taste, or preparation that, if followed, will avoid c. Enriched rice. The folic acid aromas in the enriched rice product. washing away or draining off content of rice varies from 0.008 mg/100 Thus, as proposed, the agency is enrichment ingredients. g (0.036 mg/lb) for white rice to 0.020 amending the standard of identity for As discussed above, FDA is providing mg/100 g (0.090 mg/lb) for brown rice enriched rice (§ 137.350) to include a for addition of folic acid at the level of (Ref. 7). FDA proposed to amend the range for the folic acid fortification 140 µg/100 g of the enriched cereal- standard of identity for enriched rice to level, 0.7 mg/lb to 1.4 mg/lb, with the grain products. The agency has provide for the addition of not less than lower limit being consistent with the concluded that this fortification level is 0.7 mg and not more than 1.4 mg of folic folic acid fortification level for enriched necessary to help ensure that the total acid per pound (58 FR 53305 at 53312). wheat flour. FDA concludes that use of consumption level will not exceed the The agency also noted in the standards the same minimum level of fortification recommended daily consumption level of identity proposal that rice in the is appropriate because it is consistent of 1 mg (or 1,000 µg). To minimize the United States may be enriched by with the Food and Nutrition Board’s potential losses in enrichment nutrients addition of a powder mixture containing recommendation that the same in rice, the agency had provided for a the added nutrients or by use of a rice restoration level be used for wheat flour, range in the levels, with an upper limit premix consisting of rice kernels coated corn products, and rice (although the that is twice that of the minimum level with a concentrated nutrient mix. When Food and Nutrition Board only required to be present in the rice. Thus, the powder enrichment procedure is recommended addition at restoration rice processors who use the powder- used, the label of the package generally levels). FDA is also establishing an enrichment procedure, where nutrient bears a statement that the rice should upper limit for folic acid fortification of losses would be expected to be greater, not be rinsed before or drained after enriched rice of 1.4 mg/lb, as it has done will be able to use a level of enrichment cooking, in accordance with with other enrichment nutrients added nutrients that makes it likely that § 137.350(c), to ensure that the rice to rice. As discussed in the standards of consumers will receive the minimum retains the added nutrients. However, identity proposal (58 FR 53305 at levels of nutrients required to be in the the agency stated, there is no assurance 53309), the upper level is based on the food. that these instructions are being way that rice is fortified in this country. 3. Macaroni and Noodle Products followed. In the case of the rice premix, The agency recognizes that a special coating is applied to the rice manufacturers will need time to The standards of identity for enriched kernels, so that the added nutrients will experiment with the addition of folic macaroni products (§ 139.115), enriched not be washed off if the product is acid to their products. FDA is providing nonfat milk macaroni products rinsed before cooking. Rice coated with approximately 2 years from the (§ 139.122), and enriched noodle the premix is blended with unenriched publication date of this final rule to products (§ 139.155), and the cross- rice such that the finished enriched rice allow manufacturers to test their ability referenced standards of identity for product will contain the required to comply with the new requirements enriched vegetable macaroni products minimum levels of added nutrients. The and to make appropriate label changes. (§ 139.135) and enriched vegetable agency stated that the proposed range 17. One comment stated that, because noodle products (§ 139.165), provide for would provide flexibility in the the powder-enriched rice suffers significantly higher levels of nutrient production of the enriched rice and substantial nutrient loss when it is addition than the related flour standards ensure that the food, when prepared for washed (as rice is by many consumers), of identity because these products are consumption, will contain the required it is unlikely that folate intakes will usually cooked in a large amount of minimum levels of nutrients. increase as much as FDA estimates. The water that is usually discarded after 16. According to comments on the comment suggested that the agency cooking and before consumption of the standards of identity proposal, most should, consequently, increase the macaroni and noodle products. enriched rice produced in this country fortification level. 18. One comment asserted that is manufactured using the powder FDA disagrees with the comment. For because of the preparation process for procedure to add nutrients. A comment those consumers who wish to consume macaroni and noodle products, vitamin stated that some rice processors are very ‘‘enriched’’ rice, the agency has retention data are absolutely essential concerned about the addition of an provided requirements in the standard before any level of enrichment can be enrichment powder mix containing folic of identity for enriched rice to ensure discussed. Thus, the comment acid because folic acid could result in delivery of the required nutrients. recommended that FDA delay off colors, taste, and aromas in the Section 137.350(c) requires that implementation of folic acid enriched rice. The comment maintained enrichment nutrients be present in the fortification of cereal-grain products that firms fear that consumers may rice in such form and at such levels that until more concrete information is reject the enriched rice product if it if the enriched rice is washed, it available on vitamin retention with does not possess the usual white color. contains not less than 85 percent of the cooking. It further stated that processors needed minimum quantities of the nutrients FDA is not delaying the additional time to conduct research on required to be present in the enriched implementation of folic acid the addition of folic acid to rice. rice. If they are not present in such form fortification, as suggested by the While FDA acknowledges that the or at such levels to comply with these comment, because of the need to provision in the enriched rice standard minimum requirements, the label of the increase the folic acid levels in the diets for the addition of riboflavin has been enriched rice must bear the statement of women of childbearing age. The stayed because of objections from the ‘‘to retain vitamins do not rinse before agency recognizes that there will be industry stating that riboflavin addition or drain after cooking’’ immediately losses in the content of water soluble results in a yellow discoloration being following the name of the food. In vitamins when the enriched macaroni imparted to the rice that is unacceptable addition, the label cannot bear cooking and enriched noodle products are to consumers (23 FR 1170, February 25, directions that call for washing or cooked in water, and that water is 1958), the agency has not received any draining the enriched rice. In the case drained from the foods before information from rice processors that of precooked enriched rice, the package consumption (Ref. 8). The agency also 8792 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations acknowledges that data on retention of standards, compared to those in the raised in the comments to establish an the vitamins (thiamin, niacin, and standards of identity for flour products. effective date that will provide riboflavin) required to be added to Accordingly, as proposed, FDA is manufacturers with time to implement enrich these foods are limited, and that requiring that the enriched macaroni the label and formulation changes it is difficult to make inferences as to and noodle products contain from 0.9 to required by the amendments established the retention of added folic acid when 1.2 mg/lb of folic acid. in this final rule. The agency agrees folic acid enriched products are cooked G. Effective Date with the comment that suggested that in water, and the water is discarded. FDA establish an effective date of at However, there are some data to suggest 19. Many comments expressed least 2 years from the date of that the retention rates are similar. concern over the statement in the publication of the final rule. A 2-year According to a study conducted by standards of identity proposal that the period would allow manufacturers time Ranhortra, et al. (Ref. 8), on the final rule would become effective 1 year to exhaust current packaging inventory, retention rates of the thiamin, niacin, after publication. The comments stated add folic acid to their statement of and riboflavin in three enriched pasta that it would be difficult and ingredients and the nutrition facts panel impractical to synchronize the addition products (spaghetti, noodles, and as other changes are made to update to a food of a folic acid-fortified macaroni), at least 50 percent (75 to 77 package labeling, and subsequently enriched cereal- grain product with the percent on average) of the added ensure that packaging is available that availability of revised labels for that nutrients was retained after cooking in accurately reflects the addition of folic food that declare folic acid in the water and draining. This study looked at acid to their products. Furthermore, the ingredient statement. These comments the retention of the naturally occurring agency points out that a 2-year period is pointed out that enrichment nutrients folate in the pasta products, before and consistent with the amount of time are generally not added to each after cooking, and found that the given for implementation of the separately labeled product but are retention rate was 77 to 79 percent. Nutrition Labeling and Education Act added to thousands of pounds of flour (NLEA) requirements. Thus, the Based on this data, FDA does not expect at the flour mill, the flour is sold to that the retention rate of folic acid in effective date of this final rule will be other manufacturers as an ingredient, January 1, 1998. The agency notes, these products would be significantly and then this ingredient is used in many different from the retention rates of the however, that compliance with the different products. Thus, the comments requirements established in this final other B vitamins. asserted that as a matter of economic FDA recognizes that, as with other rule may begin immediately, provided necessity, the enrichment of all these that the label accurately reflects that grain products, manufacturers will need products occurs at the same time, to conduct research on the most folic acid has been added to the regardless of the availability of new product. Furthermore, the agency will effective means of adding folic acid and labeling. One comment recommended not object to the use of stickers to bring of ensuring that the added folic acid that FDA establish an effective date of a product label into compliance with will be available in the finished food. at least 2 years from the date of the ingredient labeling and nutrition Such studies will need to focus on not publication of the final rule. The labeling provisions. The agency notes, only the method of adding the nutrient comment asserted that a 2-year period however, that unless the standardized but also on the stability of the vitamin would allow adequate time to food bears a claim about folate, the during usual conditions of distribution incorporate changes on labels of slower declaration of folate in the nutrition and storage. The agency notes that moving products as well as products label is voluntary. similar studies were required when FDA with higher retail turn rates. Thus, the 20. A few comments that raised established requirements for the comment continued, existing packaging concern about label changes that must addition of the other B vitamins to inventory could be used, thereby accompany the addition of folic acid enriched cereal-grain products. In reducing the cost impact of the suggested that the agency permit folic addition to studies, it may be necessary regulation. Another comment suggested acid to be added to the product without for manufacturers to develop label a ‘‘phase-in’’ period of at least 3 years requiring declaration in the ingredient instructions on how the product should or, in the alternative, an effective date statement. One comment contended that be prepared, e.g., instructions on consistent with the next uniform there was no safety issue regarding folic limiting the amount of water to be used effective date, whichever is later. In acid that would require its declaration in its preparation or cooking time, and support of the suggestion, the comment on the label. on whether the cooked food can be asserted that a ‘‘phase-in’’ period would Traditionally, the agency has not rinsed without loss of nutrients before allow label changes to take place permitted manufacturers who change serving, to ensure maximum retention of concurrent with the folic acid addition their formulas by adding or deleting folic acid and the added water soluble on a product-by-product basis. In ingredients to use noncompliant labels. nutrients. addition, the comment contended, such Furthermore, as discussed in response FDA is requiring the addition of folic action would allow manufacturers to to the previous comment, the agency is acid to macaroni and noodle products in exhaust their current label inventory establishing an effective date in this the same proportion as it is requiring and reduce the economic impact of the final rule that will provide industry such addition to enriched flour, except regulation. Moreover, the comment ample time to ensure that products that the required level (expressed in continued, additional time is needed for enriched with folic acid are labeled in terms of a range) will be approximately analytical testing for declaration of folic compliance with the regulations. 25 percent higher for macaroni and acid in nutrition labeling. In response to the argument that the noodle products than the required level FDA acknowledges the concerns addition of folic acid need not be of folic acid that is to be added to flour. raised in these comments regarding declared because it does not raise a This 25-percent increment is consistent label changes that must accompany the safety issue, the agency advises that the with the requirements for the other addition of folic acid to enriched cereal- act requires that all foods fabricated added nutrients (thiamin, riboflavin, grain products and to foods in which from two or more ingredients declare niacin, and iron) in the enriched these products are used as ingredients. each of its ingredients by common or macaroni and noodle products FDA is persuaded by the concerns usual name in a list of ingredients. This Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8793 requirement applies without regard to a. Health costs. Potential health costs 3. Good data on the distribution of whether there is a safety issue regarding of this regulatory option include the dietary supplement intake are not the food. Consequently, the agency has costs of neurologic disease associated available; not been persuaded by the comments to with masking of the anemia of vitamin 4. Estimates of masking of anemia permit the addition of folic acid to foods B12 deficiency. Several studies have (with subsequent progression of without also requiring that folic acid be found that folic acid can mask the neurologic symptoms) based on declared in ingredient labeling. anemia of vitamin B12 deficiency at enumerating only those associated with levels as low as 250 µg/day. Although pernicious anemia would underestimate III. Economic Impact there is no scientific consensus on the potential adverse effects because all FDA has examined the impacts of this percentage of diagnoses of vitamin B12 vitamin B12 deficiencies may lead to final rule to require the addition of folic deficiency anemia that would be neurologic problems; and acid to enriched cereal-grain products complicated by folate intake at this 5. It is difficult to predict effects of that conform to a standard of identity as level, the agency has determined that changes in dietary patterns that occur required by Executive Order 12866 and adverse health effects are not significant simultaneously with, but independently the Regulatory Flexibility Act. Executive until folate intake reaches 1 mg/day. In of, this regulation. Such changes may be Order 12866 directs agencies to assess the proposal, FDA tentatively concluded the result of educational efforts by all costs and benefits of available that the 140 µg/100 g level for various organizations, physicians, and regulatory alternatives and, when fortification of enriched cereal grain health care providers or in response to regulation is necessary, to select products was the most appropriate level health claims. regulatory approaches that maximize based on a regulation that would have The last factor is particularly net benefits (including potential required that fortification of all breakfast problematic. Recent surveys have economic, environmental, public health cereals be limited to 100 µg folic acid/ shown a growing awareness of the value and safety, and other advantages; serving. This limitation was proposed of increased folate intake among both distributive impacts; and equity). The under a separate food additive the population as a whole and, Regulatory Flexibility Act (Pub. L. 96– regulation published elsewhere in the specifically, among women of 654) requires the analysis of options for same Federal Register (58 FR 53312). childbearing age. From 1994 to 1995, regulatory relief for small businesses. With this option, 140 µg/100 g, FDA awareness of the problems associated FDA finds that this final rule is not a preliminarily concluded that intake of with insufficient folic acid intake grew significant regulatory action as defined persons in the target and nontarget from 28 to 44 percent among women of by Executive Order 12866. In populations would remain below 1 mg/ all ages (Ref. 10). As awareness grows, compliance with the Regulatory day. it is likely that folic acid intake will Flexibility Act, the agency certifies that Comments submitted in response to increase in the target group. In addition, this final rule will not have a significant the proposal to limit breakfast cereals to new label claims allowed by the final µ impact on a substantial number of small 100 g folic acid/serving persuaded the rule for health claims on the association businesses. agency to allow breakfast cereals to between folate intake and a reduced risk µ On October 14, 1993 (58 FR 53305 at continue to contain up to 400 g folic of NTD’s are also expected to increase 53309), FDA published an economic acid/serving. If all breakfast cereals were folic acid intake among women of µ impact analysis of the proposed fortified at the level of 400 g/serving, childbearing age. However, the survey requirements under the previous some high end consumers could mentioned above also showed that such awareness is strongly positively Executive Order (E.O. 12291). In the consume more than 1 mg folate/day. correlated with education, so that these analysis, the agency evaluated the However, most cereals currently are µ messages may not reach less well- following regulatory options: fortified at a level of 100 g/serving (25 educated women in the population. 1. Improve dietary practices among percent of the reference daily intake (RDI)) and only an estimated 5 percent In the folic acid health claims women of childbearing age. proposal, FDA tentatively found that 2. Require fortification with folic acid of breakfast cereals fortify at a level of µ there were several nontarget groups at 140 µg/100 g. 400 g (100 percent of the RDI). Further, it is unlikely that whose intake levels of folate may 3. Require fortification with folic acid > µ µ manufacturers of breakfast cereals will approach 1 mg/day (intakes 800 g/ at: (a) A lower level, specifically 70 g/ day) with a level of 140 µg/day and use 100 g; or (b) a higher level, specifically increase the folic acid level in cereals µ from 100 µg/serving to 400 µg/serving. of dietary supplements. These include 350 g/100 g. individuals in groups including In response to the standards of Since most breakfast cereals that contain at least 40 µg/serving (10 percent of the children 4 through 10 years of age and identity proposal, the agency received males 11 through 18, 19 through 50, and several comments that provided RDI) of folic acid can now make health claims (if all other criteria are met), 51+ years of age. Individuals at risk of information that has altered its pernicious anemia include both males economic impact analysis. Costs and manufacturers have no incentive to reformulate from 100 µg to 400 µg per and females over 51 and Hispanic benefits for each of the regulatory females ages 40 and above. The largest options are examined below. serving and incur reformulation costs. There are a number of confounding group at potential risk includes males A. Costs uncertainties that make it difficult to over 51 who take dietary supplements. estimate the potential health costs of In order to be at risk of potential adverse Cost estimates are revised first for folic acid fortification of enriched grain effects from consuming greater than 1 fortification at 140 µg/100 g followed by products (Ref. 9). These include: mg folate/day individuals must: (1) the cost estimates for fortification at 70 1. Current intakes estimated from food Consume an excessive amount of folic µg/100 g and 350 µg/100 g. consumption survey data may acid through some combination of 1. Require Fortification With Folic underestimate actual intakes due to supplements containing folic acid and Acid at 140 µg/100 g underreporting of food intake; consumption of fortified enriched grain Costs of fortifying with folic acid at 2. The folate content of foods may be products and other products containing 140 µg/100 g include health costs and underestimated due to methodologic folic acid; and (2) have low vitamin B12 reformulation costs. difficulties; status or have vitamin B12 deficiency. 8794 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations

Because of the difficulties mentioned European countries, which are (based on likelihood of a mild versus above, it is not possible to estimate the predominantly Caucasian populations. severe case) of a case of masked number of people in the high risk Although not able to estimate an pernicious anemia leading to permanent subgroup who fit all of these categories. absolute number, FDA has calculated a adverse health effects was calculated as However, one such attempt has been cost per case of neurologic symptoms the weighted mean: (0.95 × 525,598) + made between the time of the standards resulting from masking of the anemia of (0.05 × 772,598) = $537,948. of identity proposal and this final rule. pernicious anemia so that a break-even In addition to utility costs, hospital In this analysis, Romano et. al. made the point may be calculated at which point costs of neurologic effects due to following assumptions: benefits would equal the costs. The cost- pernicious anemia have been estimated 1. The annual incidence of pernicious per-illness will be calculated using the by Romano et al. (Ref. 11). In this study, anemia is 9.5 to 16.7 per 100,000 sum of medical costs and the cost of lost each neurologic case requires persons (based on two European utility. The majority of medical costs, hospitalization once for an average population-based studies); which include costs for physicians, duration of 16 days at $867/day. After 2. With low level fortification, 5 to 10 other hospital services, and drugs, are factoring in physician services and other percent of these patients would receive normally paid by insurance such that direct and indirect costs, the total direct enough folic acid to mask the anemia of estimates based on willingness-to-pay to outlay cost of neurologic disease as a avoid death would not be likely to be result of folic acid fortification was vitamin B12 deficiency; and 3. Between ‘‘24 and 26 percent of included. Other utility losses, including estimated to be $33,000 per case (Ref. patients with pernicious anemias whose death, pain and suffering, immobility, 11). Total costs per case are thus anemias respond to folic acid develop and lost productivity associated with calculated to be $570,000. However, as mentioned in Romano et neurologic signs’’ (Ref. 11). morbidity, are calculated as a function al., the cost estimate may be too high Based on these assumptions, the of the willingness- to-pay (WTP) to because these estimates assume that all authors estimated that approximately avoid death. Thus, for example, each neurologic disease would be severe, and 500 people per year would develop day of morbidity is a day spent in less than perfect health engendering some mild cases may not require neurologic disease as a result of low utility loss. That is, each day of illnesses hospitalization (Ref. 11). In addition, level folic acid fortification. Other is somewhere between a day of full this estimate may be too high if there authors contend that this estimate may utility, 1, and death, 0. Because WTP to were routine population wide screening considerably understate the number of avoid death does not include the for vitamin B12 deficiency, although this cases (Ref. 12). On the other hand, one medical expenditures mentioned above, is not currently occurring nor is it likely uncertainty not acknowledged by this these costs are calculated separately. to be instituted. At the same time, analysis is that this rule may create a The expected utility loss estimates however, the estimate may be too low if market for cereal-grain products that are were calculated in the preliminary a case leads to later complications or to not ‘‘enriched.’’ A nonstandardized economic impact analysis (the PRIA) in the need for lifelong skilled nursing care cereal-grain product could be produced the standards of identity proposal. The (Ref. 11). that was not labeled as being enriched most common symptoms of a delay in These costs, lost utility and hospital with folate (although it could have other the diagnosis of vitamin B12 deficiency costs, are not annual costs. Once vitamins and minerals added and be are permanent paresthesia (numbness or someone has experienced permanent labeled to reflect this fact) and could be tingling) in the hands or feet and ataxia adverse health effects from masked marketed to people at risk of vitamin B12 (inability to coordinate voluntary pernicious anemia, that person ought deficiency. If such a market developed, muscular movements). not to be included in the costs estimated and at-risk persons were encouraged to In the standards of identity proposal, for subsequent years, since the consume products not enriched with FDA estimated the cost per case to be discounted value of their permanent folic acid, this problem might be approximately $538,000 (Ref. 13). This adverse health effects has already been reduced. In addition, sale to high risk estimate was calculated using weighted calculated and attributed to the first subgroups of nonstandardized products probabilities of a mild (95 percent) and year. Any costs in subsequent years such as whole wheat breads (mentioned a severe case (5 percent) and the value would involve only those entering the earlier in this preamble) which do not of expected utility loss per case of at-risk age pool. need to be enriched, may increase as a neurologic disability. For each state, b. Other health costs. FDA is aware of result of this rule. mild and severe, a health status value the potential for other health problems Another uncertainty that would was calculated that related the state to resulting from increased long-term reduce the number of cases of masked a day of ‘‘perfect health’’. Thus, a person intakes of folic acid but has no data with anemia, mentioned by one comment, is with a mild case of neurologic disability which to quantify these costs. the percentage of cases of B12 deficiency is calculated to enjoy only 70 percent of c. Reformulation costs. Reformulation that could be discovered with routine the utility per day as that of a person in costs associated with this option were population screening. If such tests were a perfectly healthy state. For a more estimated in the proposal to be $27 performed proactively, B12 deficiencies severe case it would be approximately million for the first year. The cost of might be identified before neurologic 50 percent (Ref. 14). Using the likely adding the required folic acid is symptoms developed. duration of each illness, the utility loss approximately $4 million per year. The In addition, it is not clear whether the from a severe neurologic disability was cost of testing was estimated to be about European population-based studies that found to be equivalent to a loss of 5.56 $2.5 million per year and the cost of the reported the annual incidence of perfect-health years. From the value of required label changes $20 million. FDA diagnosed pernicious anemia are a perfect health year, $138,889 (Ref. 14), will use these costs for this final rule as relevant to the U.S. population. Some the value of expected utility loss per no comments were received on this part population groups in the United States case of mild neurologic disability was of the analysis. (e.g., African-American women) appear estimated to be $525,598. The utility In addition, some countries, such as to experience an earlier age-at-onset of loss due to severe neurologic disability Canada, do not allow folic acid pernicious anemia than occurs with was estimated in a similar fashion to be fortification of these products. Thus, pernicious anemia in Northern $772,598 per case. The weighted value this option would require that separate Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8795 production runs be made for fortified based on two studies, one from a high C. Conclusion products exported, to and imported risk population (Hungary) with a small In accordance with Executive Order from, these countries. This requirement number of subjects that was found to be 12866, the agency has analyzed the may preclude some manufacturers from 100 percent effective and another from economic effects of this final rule and the export market. None of the a study that showed zero risk reduction has determined that this rule, if issued, comments provided information that in a low prevalence population will not be an economically significant would assist in determining the costs of (California and Illinois). From these rule as defined by that order. having different international studies, the PHS estimated a reduction The cost of this final rule in the first requirements. of 50 percent of the number of NTD’s in year is estimated to be approximately the United States. Other studies 2. Costs of Requiring Fortification With $27 million which includes the cost of µ evaluated by PHS varied in their results. relabeling, testing, and fortification. In Folic Acid at Either 70 g/100 g or 350 A possible explanation for the lack of µg/100 g addition, there may be some health effectiveness was that studies were costs associated with neurologic The total cost of the option to fortify conducted in populations with a low symptoms resulting from masking the at 70 µg/100 g in the first year was prevalence of NTD’s which may not anemia of vitamin B12 deficiency as well estimated in the proposal to be $25 have had a folate-related subset of as the cost of separate production runs million plus the cost of separate NTD’s. for products exported to and imported In a study by Shaw et al., the production runs for these products from certain foreign countries. The cost reduction in NTD risk associated with exported to and imported from certain of the proposed action in each year after folate intake is consistent with other foreign countries. For the option of the first year should be approximately µ studies, but the reduced risk was found fortifying with folic acid at 350 g/100 25 percent of the first year cost. The to be specific to particular subsets of the g, the PRIA estimated a cost of $1.88 benefits are estimated to be between population, primarily non-Hispanic billion annually. $220 and $700 million per year. Using women and women whose education With the latter option, the folate a value of $570,000 per case of masked intake of some consumers at risk of did not exceed high school (Ref. 15). For Hispanic women, the risk reduction was pernicious anemia resulting in vitamin B12 deficiency (including neurologic damage, the break-even pernicious anemia) would be raised to approximately 10 percent. In a study by Romano et. al., the 50 percent estimate number of these cases at which costs levels exceeding 1 mg per day. One would equal benefits would fall comment to the proposal said that the of reduced risk of NTD’s was used with literature-based sensitivity limits of 67 between 386 and 1,228. estimated health costs of fortifying at Although reformulation costs of this percent (Ref. 16) and 20 percent (Refs. this (higher) level were unrealistically option are approximately $27 million, 11 and 17). high as FDA had failed to take into the cost per firm is expected to be very account that each subsequent year In the proposal, FDA estimated that µ small. Therefore, in accordance with the should only account for new cases (Ref. under the 140 g/100 g option, 116 NTD’s per year would be prevented (50 Regulatory Flexibility Act, FDA has 11). Because of the problems with determined that this rule will not have estimating numbers of people who will percent reduction). Initiation of this option was also estimated to prevent an an adverse impact on a substantial become ill at either level, FDA will not number of small businesses. quantify these costs. additional 25 infant deaths each year. Reformulation costs. In the proposal, Total benefits of this option were IV. Environmental Impact the cost of the folic acid required to estimated to be between $651 and $788 The agency has carefully considered fortify at 350 µg/100 g was estimated to million per year. the potential environmental effects of There is no consensus on the dose- be approximately $10 million per year. this action. FDA has concluded that the response relationship between folate The cost of testing was estimated to be action will not have a significant impact intake and the reduction in risk of $2.5 million and the cost of the required on the human environment, and that an NTD’s. However, using a lower bound of label changes was estimated to be $20 environmental impact statement is not 10 percent and an upper bound of a 50 million. required. The agency’s finding of no percent reduction in NTD’s, the significant impact and the evidence B. Benefits estimated reductions in total cases supporting that finding, contained in an would be between 25 (5 deaths) and 125 1. Require Fortification with Folic Acid environmental assessment, may be seen (27 deaths) resulting in quantified at 140 µg/100 g in the Dockets Management Branch benefits ranging from $220 to $700 (address above) between 9 a.m. and 4 The primary benefit of this option is million. a reduction in the number of infants p.m., Monday through Friday. born with NTD’s each year. In addition, 2. Require Fortification with Folic Acid µ µ V. References a possible benefit will be a reduction in at 70 g/100 g and 350 g/100 g The following references have been cardiovascular diseases from intake of a. 70 µg/100 g. The benefit of placed on display in the Dockets increased folate. However, there is still requiring fortification of these products Management Branch (address above) tremendous uncertainty with respect to at 70 µg/100 g was estimated in the and may be seen by interested persons the latter effect (for a more complete proposal to be between $326 and $394 between 9 a.m. and 4 p.m., Monday discussion, see folic acid food additive million. Using the sensitivity limits through Friday. document published elsewhere in this mentioned above, 10 to 50 percent of Federal Register). the estimated benefits would range from 1. Centers for Disease Control and Based on a synthesis of information $110 to $346 million. Prevention, ‘‘Recommendations for the Use from several studies, including those b. 350 µg/100 g. The benefit of of Folic Acid to Reduce the Number of Cases which used multivitamins containing requiring fortification of these products of Spina Bifida and Other Neural Tube ≥ µ Defects,’’ in Morbidity and Mortality Weekly folic acid at a daily dose level of 0.4 at 350 g/100 g is estimated to be Reports, 41, 1–7, 1992. mg, it was inferred that folic acid alone between $550 million and $1.4 billion. 2. USDA, Nationwide Food Consumption at levels of 0.4 mg per day will reduce This option is the only option that Survey/Individual Intake-1987–1988, the risk of NTD’s. This conclusion was would generate significant health costs. accession no. PB90–504044, National 8796 Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations

Technical Information Service, Springfield, List of Subjects 6. Section 137.235 is amended by VA, 1990. revising paragraph (a)(1) to read as 21 CFR Part 136 3. Food and Nutrition Board, National follows: Research Council, National Academy of Bakery products, Food grades and Sciences, Proposed Fortification Policy for standards. § 137.235 Enriched corn grits. Cereal-Grain Products, Washington, DC, 36 (a) * * * pp., 1974. 21 CFR Part 137 4. Nationwide Food Consumption Survey, Cereals (food), Food grades and (1) It contains in each pound not less Continuing Survey of Food Intakes by standards. than 2.0 milligrams (mg) and not more Individuals: Women 19–50 Years Old and than 3.0 mg of thiamin, not less than 1.2 Their Children 1–5 years, 1 day, 1985; United 21 CFR Part 139 mg and not more than 1.8 mg of States Department of Agriculture, Hyattsville, Food grades and standards. riboflavin, not less than 16 mg and not MD; NFCS, CSFII, Report No. 85–1, 1985. Therefore, under the Federal Food, more than 24 mg of niacin or 5. Subcommittee on Food Technology, Drug, and Cosmetic Act and under niacinamide, not less than 0.7 mg and Committee on Food Protection, Food and authority delegated to the Commissioner not more than 1.0 mg of folic acid, and Nutrition Board, National Research Council, of Food and Drugs and redelegated to not less than 13 mg and not more than National Academy of Sciences, Proceedings the Director, Center for Food Safety and 26 mg of iron (Fe); of a Workshop on Technology of Fortification Applied Nutrition, 21 CFR parts 136, * * * * * of Cereal-Grain Products, Washington, DC, 137, and 139 are amended as follows: May 16–17, 1977. 7. Section 137.260 is amended by revising paragraph (a)(1) to read as 6. USDA Handbook 8–20: Composition of PART 136ÐBAKERY PRODUCTS Foods, Cereal Grains, and Pasta, Raw follows: 1. The authority citation for 21 CFR Processed, Prepared. Rev., October 1989. § 137.260 Enriched corn meals. 7. Hoffpauer, D.W., ‘‘Rice Enrichment for part 136 continues to read as follows: Today,’’ Cereal Foods World, vol. 37, No. 10, Authority: Secs. 201, 401, 403, 409, 701, (a) * * * pp. 757–759, 1992. 721 of the Federal Food, Drug, and Cosmetic (1) It contains in each pound not less 8. Ranhortra, G.S., J.A. Gelroth, F.A. Act (21 U.S.C. 321, 341, 343, 348, 371, 379e). than 2.0 milligrams (mg) and not more Novak, and R.H. Matthews, ‘‘Retention of 2. Section 136.115 is amended by than 3.0 mg of thiamin, not less than 1.2 Selected B Vitamins in Cooked Pasta mg and not more than 1.8 mg of Products,’’ Cereal Chemistry, vol. 60, No. 6, revising paragraph (a)(1) to read as follows: riboflavin, not less than 16 mg and not pp. 476–477, 1985. more than 24 mg of niacin or 9. Crane, N. et al., ‘‘Evaluating Food § 136.115 Enriched bread, rolls, and buns. niacinamide, not less than 0.7 mg and Fortification Options: General Principles (a) * * * not more than 1.0 mg of folic acid, and Revisited with Folic Acid,’’ American (1) Each such food contains in each Journal of Public Health, vol. 85, No. 5, pp. not less than 13 mg and not more than pound 1.8 milligrams of thiamin, 1.1 660- 666, 1995. 26 mg of iron (Fe); 10. FDA, Health and Diet Survey, 1994 and milligrams of riboflavin, 15 milligrams * * * * * of niacin, 0.43 milligrams of folic acid, 1995. 8. Section 137.305 is amended by and 12.5 milligrams of iron. 11. Romano, P.S. et al., ‘‘Folic Acid revising paragraph (a)(1) to read as Fortification of Grain: An Economic * * * * * follows: Analysis,’’ American Journal of Public Health, vol. 85, No. 5, pp. 667–676, 1995. PART 137ÐCEREAL FLOURS AND § 137.305 Enriched farina. RELATED PRODUCTS 12. Perez-Escamilla, R., ‘‘Folic Acid (a) * * * Fortification for the Prevention of Neural 3. The authority citation for 21 CFR Tube Defects: Consensus Needed on Potential (1) It contains in each pound not less part 137 continues to read as follows: Adverse Effects,’’ American Journal of Public than 2.0 milligrams (mg) and not more Health, vol. 85, No. 11, pp. 1587–1588, 1995. Authority: Secs. 201, 401, 403, 409, 701, than 2.5 mg of thiamin, not less than 1.2 13. Healton, E.B., D.G. Savage, J.C. Brust, 721 of the Federal Food, Drug, and Cosmetic mg and not more than 1.5 mg of T.J. Garett, J. Lindenbaum, ‘‘Neurologic Act (21 U.S.C. 321, 341, 343, 348, 371, 379e). riboflavin, not less than 16.0 mg and not Aspects of Cobalamin Deficiency,’’ Medicine, 4. Section 137.165 is amended by more than 20.0 mg of niacin or vol. 7, No. 4, pp. 229–245, 1991. revising paragraph (a) to read as follows: niacinamide, not less than 0.7 mg and 14. Research Triangle Institute, ‘‘Quality of not more than 0.87 mg of folic acid, and Well-Being Scale in Estimating the Value of § 137.165 Enriched flour. not less than 13.0 mg of iron (Fe). Consumers’ Loss from Food Violating the * * * * * * * * * * FD&C Act,’’ vol. II, Final Report, 1988. (a) It contains in each pound 2.9 15. Shaw, G.M. et al., ‘‘Periconceptional milligrams of thiamin, 1.8 milligrams of 9. Section 137.350 is amended by Vitamin Use, Dietary Folate and the riboflavin, 24 milligrams of niacin, 0.7 revising paragraph (a)(1) to read as Occurrence of Neural Tube Defects,’’ milligrams of folic acid, and 20 follows: Epidemiology Resources Inc., 1995. milligrams of iron. § 137.350 Enriched rice. 16. MRC Vitamin Study Research Group, * * * * * ‘‘Prevention of Neural Tube Birth Defects: (a) * * * 5. Section 137.185 is amended by Results of the Medical Research Council revising paragraph (a) to read as follows: (1) Not less than 2.0 milligrams (mg) Vitamin Study,’’ Lancet, vol. 338, pp. 131- and not more than 4.0 mg of thiamin, 137, 1991. § 137.185 Enriched self-rising flour. not less than 1.2 mg and not more than 17. Mills, J.L., G.G. Rhoads, J.L. Simpson, * * * * * 2.4 mg of riboflavin, not less than 16 mg G.C. Cunningham, M.R. Conley, M.R. (a) It contains in each pound 2.9 and not more than 32 mg of niacin or Lassman, M.E. Walden, D.R. Depp, H.J. niacinamide, not less than 0.7 mg and Hoffman, ‘‘The Absence of a Relation milligrams of thiamin, 1.8 milligrams of Between the Periconceptional Use of riboflavin, 24 milligrams of niacin, 0.7 not more than 1.4 mg of folic acid, and Vitamins and Neural-tube Defects,’’ New milligrams of folic acid, and 20 not less than 13 mg and not more than England Journal of Medicine, 321:430–435, milligrams of iron. 26 mg of iron (Fe). 1989. * * * * * * * * * * Federal Register / Vol. 61, No. 44 / Tuesday, March 5, 1996 / Rules and Regulations 8797

PART 139ÐMACARONI AND NOODLE 21 CFR Part 172 use of folic acid on a per serving basis, PRODUCTS in accord with the Nutrition Labeling [Docket No. 91N±100F] and Education Act of 1990; (2) allow for 10. The authority citation for 21 CFR Food Additives Permitted for Direct the addition of folic acid in foods for part 139 continues to read as follows: Addition to Food for Human which standards of identity exist, where Authority: Secs. 201, 401, 403, 409, 701, Consumption; Folic Acid (Folacin) such standards permit the addition of 721 of the Federal Food, Drug, and Cosmetic folic acid; (3) restrict to breakfast cereals Act (21 U.S.C. 321, 341, 343, 348, 371, 379e). AGENCY: Food and Drug Administration, the foods for which standards of HHS. 11. Section 139.115 is amended by identity do not exist, to which folic acid revising paragraph (a)(1) to read as ACTION: Final rule. may be added; (4) continue to permit follows: the use of folic acid in infant formulas, SUMMARY: The Food and Drug dietary supplements, and foods for § 139.115 Enriched macaroni products. Administration (FDA) is amending the special dietary use; and (5) incorporate food additive regulations to provide for (a) * * * specifications for folic acid consistent the safe use of folic acid in foods that with those in the Food Chemicals (1) Each such food contains in each are the subject of a standard of identity pound not less than 4.0 milligrams (mg) Codex. that requires the addition of folic acid; Interested persons were given until and not more than 5.0 mg of thiamin, to provide for its addition to breakfast not less than 1.7 mg and not more than December 13, 1993, to comment on the cereals on a per serving basis; to permit proposal. FDA received 59 letters, each 2.2 mg of riboflavin, not less than 27 mg its use in infant formulas, medical and not more than 34 mg of niacin or containing one or more comments, from foods, and foods for special dietary use; consumers, members of the Folic Acid niacinamide, not less than 0.9 mg and and to incorporate specifications for not more than 1.2 mg of folic acid, and Subcommittee of FDA’s Food Advisory folic acid consistent with those in the Committee, the United States not less than 13 mg and not more than Food Chemicals Codex. This action is 16.5 mg of iron (Fe); Pharmacopeial Convention, Inc., being taken to ensure that the amount of consumer interest groups, food * * * * * folic acid that all segments of the manufacturers, trade associations, and 12. Section 139.122 is amended by population are reasonably expected to dietary supplement manufacturers. Most revising the first sentence of paragraph consume is safe under the Federal Food, comments generally supported the (a)(3) to read as follows: Drug, and Cosmetics Act (the act) and to proposed amendments. Some comments implement Public Health Service’s § 139.122 Enriched nonfat milk macaroni suggested modifications of various products. (PHS) recommendation to increase folic provisions of the proposed rule or acid intake by women of childbearing requested clarification of certain issues. (a) * * * age, thereby reducing the risk of (3) Each such food contains in each A number of comments were received pregnancies affected by neural tube that were more appropriate to other pound not less than 4.0 milligrams (mg) defects (NTD’s). and not more than 5.0 mg of thiamin, dockets, and these were forwarded to DATES: Effective March 5, 1996; written the appropriate dockets (Docket Nos. not less than 1.7 mg and not more than objections and requests for a hearing by 2.2 mg of riboflavin, not less than 27 mg 91N–100H or 91N–100S) for response. A April 4, 1996. The Director of the Office summary of the comments and the and not more than 34 mg of niacin or of the Federal Register approves the niacinamide, not less than 0.9 mg and agency’s responses are presented in incorporation by reference in section II of this document. not more than 1.2 mg of folic acid, and accordance with 5 U.S.C. 552(a) and 1 not less than 13 mg and not more than CFR part 51 of a certain publication in II. Comments to the Proposal 16.5 mg of iron (Fe). * ** 21 CFR 103.35(d)(3)(v), effective March A. Safe Upper Limit * * * * * 5, 1996. 13. Section 139.155 is amended by As part of FDA’s implementation of ADDRESSES: Submit written objections to the PHS recommendation that women of revising paragraph (a)(1) to read as the Dockets Management Branch (HFA– follows: childbearing age consume 400 305), Food and Drug Administration, micrograms (µg) of folic acid per day to § 139.155 Enriched noodle products. 12420 Parklawn Dr., rm. 1–23, reduce their risk of a pregnancy affected Rockville, MD 20857. (a) * * * by an NTD (Ref. 1), FDA initiated this FOR FURTHER INFORMATION CONTACT: (1) Each such food contains in each proceeding, as well as a rulemaking to Dennis M. Keefe, Center for Food Safety pound not less than 4 milligrams (mg) authorize a health claim on the and Applied Nutrition (HFS–206), Food and not more than 5 mg of thiamin, not relationship between folate and NTD’s and Drug Administration, 200 C St. SW., less than 1.7 mg and not more than 2.2 and a rulemaking to require the addition Washington, DC 20204, 202–418–3090. mg of riboflavin, not less than 27 mg of folic acid to certain standardized and not more than 34 mg of niacin or SUPPLEMENTARY INFORMATION: cereal-grains. As part of FDA’s rulemaking to authorize a folate health niacinamide, not less than 0.9 mg and I. Background not more than 1.2 mg of folic acid, and claim, the agency found it necessary to not less than 13 mg and not more than In the Federal Register of October 14, address the issue of the safe upper limit 16.5 mg of iron (Fe); 1993 (58 FR 53312), FDA proposed to of daily folate intake. In the health claim amend the regulation that establishes proceeding, FDA was confronted with * * * * * Dated: February 26, 1996. safe conditions of food use for folic acid, all of the issues related to a safe upper § 172.345 (21 CFR 172.345)). In the limit that have been presented in this David A. Kessler, proposed rule, which was entitled proceeding. Thus, FDA’s response to the Commissioner of Food and Drugs. ‘‘Food Additives Permitted for Direct comments that addressed the safe upper Donna E. Shalala, Addition to Food for Human limit for folic acid intake in the present Secretary of Health and Human Services. Consumption; Folic Acid (Folacin),’’ rulemaking draws largely on the [FR Doc. 96–5014 Filed 2–29–96; 12:03 pm] FDA said that it intended to amend agency’s response to similar comments BILLING CODE 4160±01±P § 172.345 to: (1) Set limitations on the as laid out in a final rule authorizing a