Food Standards: Amendment of Standards of Identity For Enriched Grain Products to Require Addition of Folic Acid

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 136, 137, and 139

[Docket No. 91N-100S]

RIN 0910-AA19

Food Standards: Amendment of Standards of Identity For Enriched

Grain Products to Require Addition of Folic Acid

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the

standards of identity for several enriched grain products and, by

cross-reference, the standards of identity for enriched bromated flour,

enriched vegetable macaroni, and enriched vegetable noodle products, to

require the addition of folic acid. The agency is requiring that these

products be fortified with folic acid at levels ranging from 0.43

milligrams (mg) to 1.4 mg per pound (mg/lb) or 95 micrograms

(g) to 309 g/100 grams (g), of product. These values

are based on a fortification level of 140 g/100 g (0.635 mg/

lb) of the cereal grain product. This action is being taken to help

women of childbearing age to reduce their risk of having a pregnancy

affected with spina bifida or other neural tube defects (NTD's) and to

comply with the recommendation of the U.S. Public Health Service (PHS)

that they consume at least 0.4 mg (400 g) of folic acid daily.

This action also responds to a citizen petition submitted by Glenn

Scott.

EFFECTIVE DATE: January 1, 1998.

FOR FURTHER INFORMATION CONTACT: Felicia B. Satchell, Center for Food

Safety and Applied Nutrition (HFS-158), Food and Drug Administration,

200 C St. SW., Washington, DC 20204, 202-205-5099.

SUPPLEMENTARY INFORMATION:

I. Background

Recent estimates state that there are approximately 4,000

pregnancies each year, including 2,500 live births, that are affected

by spina bifida and other neural tube defects. In September 1992, PHS

recommended that all women of childbearing age in the United States

consume 0.4 mg (400 g) of folic acid daily to reduce their

risk of having a pregnancy affected with spina bifida or other NTD's

(Ref. 1). Furthermore, PHS identified several possible approaches by

which folate intake by the target population could be increased. These

approaches included: (1) Improvement of dietary habits, (2)

fortification of the U.S. food supply, and (3) daily use of folic acid

supplements by women throughout their childbearing years. However, the

PHS recommendation cautioned against daily intakes of folate above 1

mg. A recognized adverse effect of high intakes of folate is a masking

of the anemia of vitamin B12 deficiency, allowing the neurologic damage

to progress untreated. PHS noted that care should be taken to keep

total folate consumption at less than 1 mg (1,000 g)/day,

except under the supervision of a physician (Ref. 1).

Following publication of the PHS recommendation, FDA convened a

Folic Acid Subcommittee from its Food Advisory Committee (hereinafter

referred to as the Folic Acid Subcommittee) to consider some of the

issues raised by the recommendation. After consideration debate, the

Folic Acid Subcommittee identified several approaches that might assist

women of childbearing age to increase their daily folate intake. These

approaches included: (1) Development of a fortification program such

that 90 percent of women of childbearing age could receive at least 400

g per day from all sources, while preventing

[[Page 8782]]

excessively high folate intakes by nontarget groups; (2) appropriate

labeling of foods, including dietary supplements; and (3)

implementation of an educational program directed primarily at women of

childbearing age that emphasizes the importance of folate intake before

pregnancy, and continuing into early pregnancy and its potential effect

on reducing the incidence of NTD's. (For a detailed discussion of the

issues and concerns raised by the Folic Acid Subcommittee please refer

to the Health Claims proposed rule (58 FR 23254 at 23256) and the final

rule authorizing a health claim about the relationship between folate

and neural tube defects (hereinafter referred to as the claims final

rule) published elsewhere in this issue of the Federal Register.)

After considering the suggestions of PHS and the Folic Acid

Subcommittee, FDA tentatively concluded that development and

implementation of a fortification program for the addition of folic

acid to the food supply could be an effective part of an overall plan

to increase the folate intake of women of childbearing age to assist

them in reducing their risk of having a NTD-affected pregnancy. Food

fortification, as noted by the Folic Acid Subcommittee and expert

speakers who testified before the Folic Acid Subcommittee, has the

advantage of reaching a great number of women in the target population

before conception and during early pregnancy. It also has the advantage

of providing folic acid in a continuous and passive manner and, thus,

represents a potentially effective means for improving the folate

nutriture of women throughout their childbearing years. However,

fortification must be controlled to ensure that daily intake of folate

by the target population, as well as by the general population, is no

more than 1 mg.

The issues raised by a fortification program were highlighted for

the agency in the Federal Register of October 14, 1993 (58 FR 53254),

in a document entitled ``Food Labeling: Health Claims and Label

Statements; Folate and Neural Tube Defects,'' (hereinafter referred to

as the folic acid health claims proposal) when it proposed to authorize

a health claim about the relationship between folate and the risk of

neural tube birth defects on the labels or in the labeling of foods and

dietary supplements. In the folic acid health claims proposal (58 FR

53254 at 53270), FDA acknowledged that authorizing a health claim on

folate and NTD's would create the likelihood that manufacturers would

fortify their products with folic acid so that they could qualify to

bear the claim, thereby increasing the possibility of uncontrolled

fortification of the food supply. Consequently, FDA said that any

fortification program that it adopted must be consistent with a safe

range of intake for all population groups and yet be capable of

maximizing the folate intakes of the target population within this safe

range.

The options that FDA considered for providing folic acid to women

of childbearing age through food fortification included the addition of

folic acid to cereal-grain products, fruit juices, and dairy products.

In weighing these options, FDA considered the effects of the inclusion

of folic acid in breakfast cereals and in dietary supplements. The

agency's decision to factor the amount of folic acid supplied by

breakfast cereals and supplements in its estimates of the effects of

fortification is fully discussed in the folic acid health claims

proposal (58 FR 53254 at 53276).

In determining the appropriate levels of fortification with folic

acid, the agency used the U.S. Department of Agriculture's (USDA's)

1987 to 1988 national food consumption data (Ref. 2) to estimate the

daily intake of folate for the target population, as well as for the

general population, with fortification at different levels for cereal-

grain products, dairy products, and juices. The agency estimated the

effects of fortification using three values: 70, 140, and 350

g of folic acid/100 g of cereal- grain product. As discussed

in the folic acid health claims proposal, the value of 70 g/

100 g (0.317 g/lb) is the amount recommended in 1974 by the

Food and Nutrition Board, National Research Council, National Academy

of Sciences, and would restore the folate lost in the milling of

cereal-grain products (Ref. 3). The value of 140 g/100 g is

twice that amount, and 350 g/100 g is five times that amount.

FDA's analysis showed that when fortification included fruit juices

and dairy products in addition to cereal-grain products, ready-to-eat

breakfast cereals, and dietary supplements, intakes by consumers in

some nontarget groups exceeded 1 mg/day even at the lowest level of

fortification. However, when fortification is limited to cereal-grain

products at levels of 70 g/100 g or 140 g/100 g,

estimates of daily intakes remained below 1 mg/100 g. At fortification

levels of 350 g/100 g, FDA estimated the daily intake to reach

levels of 1,220 g/day, which exceeds the recommended safe

upper limit.

The agency also estimated the daily intake of folate for consumers

who follow Federal government dietary guidance, such as the U.S.

Dietary Guidelines and the DHHS/USDA Food Guide Pyramid, and consume

cereal-grain products fortified with folic acid, to determine whether

these consumers will have daily intakes in excess of the recommended

safe upper limit of 1 mg/day.

These estimates showed that consumers who followed even the low-end

of recommendations from the USDA Food Guide Pyramid could, without

supplement use, easily consume 420 g or more of folate per day

from cereal-grain products fortified with 70 g/100 g. Further,

such consumers' daily intake could triple if such products were

fortified with 350 g folic acid/100 g.

As a result of its analysis of fortification of several cereal-

grain, dairy, and juice products, FDA tentatively determined that

fortification should be limited to cereal-grain products and not

extended to dairy products and fruit juices. The agency noted that

intakes by very large segments of the general population could reach

several milligrams per day if all of these foods were fortified with

folic acid.

The agency also tentatively decided that the appropriate

fortification level for cereal-grain products was 140 g/100 g.

Based on the results of its analysis, FDA determined that fortification

of cereal-grain products with 140 g/100 g, along with

fortification of ready-to-eat breakfast cereals up to 100 g/

serving and dietary supplements up to 400 g per unit or per

serving, would provide increased intakes of folate for women in their

childbearing years, while keeping daily intakes for the nontarget

population within the recommended safe upper limit of approximately 1

mg/day. The agency noted that even with supplement use, 95th percentile

intakes by adults 51+ years of age could reach 840 to 860 g/

day if these enriched cereal-grain products are fortified with 140

g/100 g. While the agency recognized that this level

approached the recommended safe upper limit and did not take into

account likely underreporting biases regarding food intakes and

underestimation of folate content of foods, it tentatively concluded

that fortification of cereal-grain products with 140 g/100 g

folic acid was the most appropriate fortification level of the three

levels analyzed.

In addition to estimating daily intakes of folate at the levels

cited above, FDA reviewed the existing food additive regulation

Sec. 172.345 (21 CFR 172.345) governing the use of folic acid to

determine whether the regulation was adequate to ensure that addition

of folic acid to foods would be consistent with

[[Page 8783]]

the fortification proposals discussed above. As a result of its review,

FDA recognized that the existing regulation lacked the guidance

necessary for manufacturers to decide which foods are appropriate for

fortification, and the levels at which folic acid can be added. More

importantly, FDA realized that the regulation would not have limited

the addition of folic acid to enriched cereal-grain products, breakfast

cereals, and dietary supplements. In fact, the regulation as written

would have permitted folic acid addition to virtually any food.

Thus, in the same issue of the Federal Register that the agency

proposed to authorize a health claim about the relationship of folate

and NTD's (58 FR 53254 at 53270), it published a proposal entitled

``Food Additives Permitted for Direct Addition to Food for Human

Consumption, Folic Acid (Folacin)'' (58 FR 53312) (hereinafter referred

to as the food additives proposal) to amend the food additive

regulation to restrict the addition of folic acid to specific foods. In

that document, FDA proposed, among other things, to establish a

limitation on the addition of folic acid to breakfast cereals of 100

g folic acid per serving, to retain current limitations (i.e.,

400 g/daily) on the use of folic acid in dietary supplements,

and to permit the addition of folic acid to foods as authorized by the

standards of identity. The agency tentatively concluded that such

action was necessary to establish safe conditions of use for folic acid

in the food supply and still assist the target population, women of

childbearing age, to achieve the goal recommended by PHS that they

consume at least 400 g of folate per day.

Also, in the October 14, 1993, issue of the Federal Register, FDA

published a proposal entitled ``Food Standards: Amendment of the

Standards of Identity for Enriched Grain Products to Require Addition

of Folic Acid,'' (58 FR 53305) (hereinafter referred to as the

standards of identity proposal) to amend the following standards of

identity to require the addition of folic acid at a fortification level

of 140 g/100 g: enriched bread, rolls, and buns (Sec. 136.115

(21 CFR 136.115)); enriched flour (Sec. 137.165 (21 CFR 137.165));

enriched self-rising flour (Sec. 137.185 (21 CFR 137.185)); enriched

corn grits (Sec. 137.235 (21 CFR 137.235)); enriched corn meals

(Sec. 137.260 (21 CFR 137.260)); enriched farina (Sec. 137.305 (21 CFR

137.305)); enriched rice (Sec. 137.350 (21 CFR 137.350)); enriched

macaroni products (Sec. 139.115 (21 CFR 139.115)); enriched nonfat milk

macaroni products (Sec. 139.122 (21 CFR 139.122)); and enriched noodle

products (Sec. 139.155 (21 CFR 139.155)) and, by cross-reference, the

standards of identity for enriched bromated flour (Sec. 137.160 (21 CFR

137.160)), enriched vegetable macaroni products (Sec. 139.135 (21 CFR

139.135)), and enriched vegetable noodle products (Sec. 139.165 (21 CFR

139.165)).

FDA received approximately 170 letters in response to its proposal

to amend the standards of identity for enriched cereal-grain products

to require folic acid fortification at 140 g/100 g. Each

letter contained one or more comments. The letters were from a wide

range of sources, including individual members of FDA's Folic Acid

Subcommittee and Food Advisory Committee, Federal and State Government

agencies, a foreign government, health care organizations, academia,

consumer organizations, medical professionals, consumers, industry, and

industry trade associations. Some comments supported various provisions

of the proposal. Other comments suggested modifications, revisions, or

revocations of various provisions of the proposal. Some comments raised

concerns that were more germane to issues discussed in the folic acid

health claims and food additive proposals. These comments were

forwarded to the appropriate dockets for response. Some comments raised

issues that were outside the scope of this rulemaking and will not be

addressed in this final rule. A summary of the relevant comments, the

agency's responses to the comments, and a complete discussion of the

agency's conclusions with respect to the fortification of enriched

cereal-grain products follow.

II. Comments and Agency Response

A. Fortification

1. The majority of comments recognized the need to assist women of

childbearing age to increase their daily intake of folate to reduce

their risk of an NTD-affected pregnancy. Many of these comments agreed

with the PHS' and Folic Acid Subcommittee's recommendations that

fortification of the food supply is an appropriate approach to achieve

this goal. Several comments, however, opposed the use of fortification

as a mechanism to address this need. Some of the comments opposed

fortification because of uncertainties in the efficacy data. These

comments stated that the available data do not indicate what minimum

level of folate is needed to effect a significant reduction in NTD's,

and they argued that, therefore, the decision to fortify is premature.

These comments suggested that the agency wait until additional studies

have been completed that better define the minimum level of folate

needed to be effective or that identify other alternatives that would

be effective in increasing the daily folate intake of the target

population.

While FDA recognizes that there is some uncertainty in the

literature as to the optimal intake of folate required to reduce the

risk of NTD's, PHS, in examining the data from the available human

studies, found the evidence sufficiently consistent to make its

recommendation that all women capable of becoming pregnant should

consume 400 g folic acid daily. This target intake goal

represents the best scientific judgment based on available data. It has

also been supported by the Folic Acid Subcommittee.

Furthermore, PHS, the Folic Acid Subcommittee, as well as other

medical experts, recommended food fortification as part of an overall

program to improve the folate intake of women of childbearing age. This

recommendation is based on the fact that 50 percent of pregnancies are

unplanned, and that a large segment of women in the target group will

not use folic acid supplements daily. Thus, a passive means of ensuring

that these women have adequate folate intake is important. The comments

that opposed fortification did not submit any data in support of their

position. Thus, the agency has no basis to reject the recommendations

of PHS and the Folic Acid Subcommittee to develop a folate

fortification program to assist women of childbearing age in consuming

at least 400 g/day.

Although the agency is aware that there are several ongoing studies

on the relationship between folate and NTD's, it has not been persuaded

by the comments to wait until additional studies have been completed to

determine what minimum level of folate intake is likely to be

effective. The agency has confidence in the data that suggest that at

intake levels of 400 g/day, the incidence of NTD's can be

reduced. Thus, the agency concludes that it would not be in the best

interest of women in the target group to wait until these studies are

completed and reviewed before implementing a program to assist them in

increasing their daily intake of folate.

The evidence that is available supports the position that the

consumption of folate plays an important role in reducing the risk of

neural tube birth defects. Weighing this evidence and recognizing that

the majority of women in the target population do not consume the

levels of

[[Page 8784]]

folic acid recommended to reduce the risk of neural tube birth defects

(Ref. 1), the agency concludes that it is appropriate to implement a

fortification program at this time.

Further, the agency is concerned that without the limitations that

it is adopting in this final rule, and in the final rule entitled

``Food Additives Permitted for Direct Addition to Food for Human

Consumption; Folic Acid (Folacin)'' (hereinafter referred to as the

food additives final rule) which is published elsewhere in this issue

of the Federal Register, to control the addition of folic acid to the

food supply, the authorization of the health claim about folate and

NTD's may encourage overfortification of the U.S. food supply and

increase the risk of overconsumption of folate. Because the current

food additive regulation does not limit or specify the types of foods

that can be fortified with folic acid, approval of the claim, without

any other action by the agency, could encourage manufacturers to

fortify a variety of foods to qualify the food for a health claim.

Consequently, without proper control over the types of foods that can

be fortified with folic acid, overfortification could result.

The amendment to the standards of identity for enriched cereal-

grain products to require the addition of folic acid at specific levels

will help to ensure that the addition of folic acid to the food supply

is done in a safe, rational, and reasonable manner because it will

limit the number of foods that can be fortified and limit the level of

fortification. The levels of fortification established in this final

rule, coupled with the provisions governing addition of folic acid to

nonstandardized foods established in the food additives final rule,

will meet the goal of increasing folate intake among women of

childbearing age while keeping the daily consumption of folate below

the safe upper limit of 1 mg/day.

2. Comments that opposed fortification asserted that consumers

believe that fortification as proposed denies freedom of choice and

control over daily folate intake and is, therefore, viewed as an

attempt to medicate people without obtaining informed consent. These

comments further asserted that fortification, as proposed, subjects

them to the risk of overconsumption. As an alternative, these comments

suggested that the effort to increase dietary folate intake in the

target population focus on the use of dietary supplements because the

amount of intake can be better controlled. They suggested that FDA work

with other public health service agencies to establish policy

initiatives equivalent to those used by the food and dietary supplement

industries to market their products.

The agency disagrees with these comments. The agency is providing

for fortification with folic acid only in the standards of identity for

enriched cereal-grain products. Unenriched cereal-grain products

without folic acid will continue to be available. Consumers will be

able to select foods made with the unenriched version of the product if

they wish to avoid folic acid. Furthermore, the estimated daily intakes

that will result from the level of fortification established in this

final rule are well below the level of folic acid traditionally used to

treat persons with folate deficiency. Therapeutic dosages of folic acid

used for treatment of folate deficiency are generally in the range of 1

to 5 mg/day and are administered under the supervision of a physician.

Therefore, the comments that suggest that fortification of enriched

cereal-grain products is an attempt to medicate the U.S. population

simply have no basis in fact.

Furthermore, the intakes that are likely to result from the level

of fortification established in this final rule do not present a health

concern to the general population, especially in conjunction with the

provisions of the food additive final rule published elsewhere in this

issue of the Federal Register. FDA has projected the total daily intake

of folate that is likely to result from the levels of fortification

that FDA is requiring and determined that it is well within the safe

upper limit of intake. Moreover, cereal-grain products have a long

history of being vehicles for improving the nutrient intake of the U.S.

population. FDA requires the addition of niacin, thiamin, and

riboflavin in the standards of identity for enriched cereal-grain

products to improve the daily intake of these nutrients. Fortification

of these products was instrumental in reducing the prevalence of

diseases related to insufficient intake of these vitamins.

In response to the comments that suggested that FDA rely on the use

of dietary supplements to increase daily folate intake, the agency

notes that in requiring the fortification of enriched cereal-grain

products, it is not discounting the use of dietary supplements to

assist women in the target group to increase their daily folate intake.

In fact, the agency included the use of dietary supplements in its

estimates to determine the appropriate level for fortification of

enriched cereal-grain products. However, the agency is not confident

that the use of dietary supplements alone will be sufficient to reach

the target population when folate intake is critical (i.e., before and

during the first 6 weeks of pregnancy).

During the first 6 weeks of pregnancy many women are not even aware

that they are pregnant and would likely not be under the care of a

physician. Thus, as stated in several comments, there would be no

reason to expect the many women who do not normally take supplements

daily to be motivated to change this behavior. Therefore, supplement

use cannot be relied on as the sole source for increasing dietary

folate intake. As discussed above, the use of fortification of cereal-

grain products has the advantage of providing folic acid in a

continuous and passive manner and, therefore, should be an effective

means for improving the folate nutriture of women in their childbearing

years.

3. A few comments opposed to fortification suggested that, as an

alternative, FDA encourage women in the target group to increase their

daily folate intake by increasing consumption of foods that naturally

contain high levels of folate such as blackeye peas.

While FDA finds merit in the comments' suggestion to encourage

women in the target group to increase their daily folate intake by

increasing their consumption of foods naturally high in folate, the

agency is not persuaded that such action makes food fortification

unnecessary. The dietary guidance suggested by the comment can be used

in conjunction with food fortification, as part of a program designed

to help women in the target group to increase their daily folate

consumption. A health claim about the relationship between folate and

NTD's on a food that qualifies to bear the claim will contribute to

such a program, regardless of whether the food naturally qualifies to

bear the claim or qualifies on the basis of its fortification level. In

addition, foods that naturally contain folate and qualify to bear a

health or nutrient content claim are likely to be highlighted as a

source of this nutrient. Such claims will encourage women in the target

group to select these foods as a part of their diet.

Most significantly, however, given the value of adequate folate

intake by women of childbearing age and given the value of a program

that allows women to obtain adequate folate by simply consuming such

staples as bread and rolls, FDA sees no reason not to require

fortification of such foods, even though foods exist that are naturally

high in folate.

4. Some comments opposed to fortification opined that fortification

[[Page 8785]]

would not assure physicians and health care professionals that their

patients are obtaining adequate amounts of folate from the food supply

because the bioavailability of folate in foods is 25 to 75 percent

depending on the food.

As discussed in the folic acid health claims proposal, FDA

considered several issues in developing its options for fortification.

With respect to issues of bioavailability, FDA concluded that

bioavailability cannot be meaningfully factored into fortification

scenarios because issues of bioavailability are very complex, and no

systematic data are available on many of the factors that affect

bioavailability. Consequently, the estimates developed by FDA focused

more on consumption patterns of various staple foods, and their

availability and use in the U.S. food supply, than on the

bioavailability of folic acid from a specific food.

The comment did not provide information to persuade the agency that

the complexity associated with bioavailability would significantly

reduce the effectiveness of food fortification as part of an overall

effort to improve folate nutriture among women in the target group.

5. Two comments recommended revising the proposal to require the

addition of vitamin B12 in a one-to-one ratio with folic acid. The

comments contended that doing so will not only prevent vitamin B12

deficiency, but it will also prevent the masking effect that may be

caused with high consumption of folate. One comment urged FDA to design

research that will determine the safety and effectiveness of fortifying

the food supply with vitamin B12 along with folic acid because

such fortification could eliminate the adverse effect of folate on

vitamin B12 deficiency.

The agency is not persuaded that the approach suggested by these

comments addresses all of the safety concerns relating to persons with

vitamin B12 deficiencies. As fully discussed in the food additives

final rule, FDA rejects this recommendation because the available data

do not establish that requiring the addition of vitamin B12

whenever folic acid is added will eliminate the safety concerns

relating to persons with vitamin B12 deficiencies that arise

because of deficiencies in intrinsic factor (pernicious anemia) or

other B12-related deficiencies.

6. Two comments opposed to fortification stated that FDA should

take the same position with respect to folic acid fortification that it

did when it decided not to fortify foods with iron in the 1970's

because of the concern about iron storage diseases.

While the agency acknowledges that it considered taking a similar

approach to increase the amount of iron provided by the diet when it

proposed to double the amount of iron added to enriched cereal-grain

products, the agency did not finalize that proposal because of

significant safety concerns regarding the risk of iron storage

diseases. Rather, the agency retained the existing level of iron

fortification for cereal-grain products. The agency does not have

similar safety concerns about the level of folic acid fortification

that it is requiring in this final rule because it has concluded, based

on a safety review (as fully discussed in the food additives proposal

and final rule), that this required level is safe and will not result

in overconsumption of folate.

B. Covered Products

7. Some comments stated that dietary consumption studies indicate

that women of reproductive age are less likely than other groups to

consume enriched cereal-grain products that conform to a standard of

identity, and that, therefore, the use of such foods as a vehicle for

folic acid fortification would not significantly affect the risk of

NTD's. These comments argued that, instead, fortifying these foods will

only increase the amount of daily folate intake among the nontarget

groups.

In selecting cereal-grain products as vehicles for fortification,

the agency started with the basic principle that fortification of

staple products that are commonly consumed in significant amounts by

virtually all members of the target population is most likely to result

in increased intakes of a specific nutrient by the target population.

Although the agency recognizes that current survey data suggest that

consumption of enriched grain products may be somewhat lower in the

target population than in other groups, these foods still are reported

to be consumed on a daily basis by more than 90 percent of women of

childbearing age (Ref. 4). In addition, data show that the difference

between target and nontarget populations in consumption of other foods

considered as fortification vehicles, such as dairy products and

juices, is even greater (Ref. 4). Therefore, the other foods would be

no more appropriate as fortification vehicles for maximizing folate

intake by the target group, and yet maintaining safe consumption by

nontarget groups, than cereal-grain products.

The agency notes that cereal-grain products were recommended by the

Food and Nutrition Board in its 1974 report on food fortification as

fortification vehicles because of the patterns of consumption of these

foods. In addition, enriched cereal-grain products have a long history

of being successful vehicles for improving the nutriture of the U.S.

population and for reducing the risk of nutrient deficiency diseases.

Thus, the agency concludes that enriched cereal-grain products are an

appropriate vehicle to increase daily folate intake among women of

childbearing age. In fact, the estimates that FDA developed in

evaluating options for folic acid fortification demonstrate that the

addition of folic acid to enriched cereal-grain products, coupled with

the addition of this nutrient to breakfast cereals and dietary

supplements, will help to significantly increase the daily folate

intake of women in the target group (see Table 7 of 58 FR 53254 at

53295)).

Furthermore, increasing awareness of the role of folate in reducing

the risk of neural tube birth defects through the use of health claims

and other educational initiatives should encourage women in the target

group to increase their daily folate intake by consuming folate

containing foods, including enriched cereal-grain products. Consumption

of cereal-grain products is also likely to be influenced by current

dietary guidelines that promote increased consumption of these foods.

8. Other comments requested that FDA permit the addition of folic

acid to other cereal-grain products such as whole grain flours, breads,

cereals, macaroni products, rice, and grits and not just the enriched

cereal-grain foods that conform to a standard of identity. The comments

argued that without these products being fortified, consumers may be

encouraged to eat enriched refined grains instead of their whole grain

counterparts and consequently follow dietary patterns that are

inconsistent with current dietary guidelines to eat whole grain

products.

FDA did not propose to provide for the addition of folic acid to

whole grains or products from whole grains because, traditionally,

these products are not enriched. Whole grain wheat products naturally

contain higher levels of the B vitamins, including folate, because the

germ and bran layer are not removed when the wheat kernel is processed.

FDA's standards of identity for cracked wheat, crushed wheat, and whole

wheat flour, in Secs. 137.190, 137.195, and 137.200, respectively,

state that the proportions of the natural constituents of such wheat,

other than the moisture, remain unaltered by the manufacturing process.

In establishing the standards of identity for the enriched cereal-grain

products, the agency's initial goal was to

[[Page 8786]]

restore thiamin, niacin, and riboflavin, nutrients that are removed

when the bran layer and germ are removed during the processing of

wheat. Subsequently, the agency required the addition of iron to the

enriched grain and also provided for the optional addition of other

nutrients, such as calcium and vitamin D.

The estimates that the agency has relied on in selecting a

fortification level of 140 g/100 g considered only

fortification of breakfast cereals, dietary supplements, and

standardized enriched cereal grain products and did not include

fortification of other nonstandardized or unenriched standardized

cereal-grain products. Consequently, including such foods in the

fortification program could result in a daily intake of folate that is

above the safe upper limit of 1 mg/day. Thus, the agency is not

persuaded by the comment that other cereal-grain products should be

fortified with folic acid.

With regard to the concern raised in the comment that fortification

of enriched cereal grain products may encourage consumers to choose

these products over their whole grain counterparts, the comment did not

provide any support for its concern. The decision to fortify enriched

cereal grain products at the level of 140 g/100 g is based on

current dietary consumption patterns. The agency is not persuaded by

the comments that the addition of folic acid will significantly change

consumption patterns of the target population. There is no evidence

that women will suddenly start consuming enriched products instead of

whole grain foods. In fact, one reason the agency has decided to

require the fortification of enriched cereal-grain products is to

enable women of childbearing age to significantly increase their daily

folate intake without changing their dietary habits. Finally, the

agency notes that while current dietary recommendations do encourage

increased consumption of whole grain foods, they also encourage

consumption of all cereal-grain products.

9. One comment expressed concern that the agency's tentative

decision to fortify cereal-grain products was unfair to the cereal-

grain industry because it singled out one segment of industry to

address a health concern. (The agency notes that the comment was not

submitted by a member of the cereal grains industry.)

As discussed in the folic acid health claims proposal, FDA

considered several options that included fortification of dairy

products and juices before concluding that the most appropriate option

was to limit fortification to enriched cereal-grain products. Aside

from the fact that these products have a long history of successful use

as vehicles for increasing nutrient intake among U.S. consumers,

consumption data and other relevant information reviewed by the agency

show that these products are consumed routinely on a daily basis by 90

percent of women in the target group. Furthermore, some comments

submitted to the docket by representatives of the cereal grains

industry stated that, generally, these products can be easily fortified

with folic acid. Therefore, FDA concludes that the enriched cereal-

grain products are the appropriate foods for fortification, and that

fortification of these products is not unfair to the industry.

C. Fortification Level

10. In the standards of identity proposal, FDA requested comments

on whether the proposed fortification levels discussed for enriched

cereal-grain products were appropriate. Comments responding to this

issue were varied. Some comments that supported fortification of

cereal-grain products stated that the proposed levels were too low to

have any appreciable effect on reducing the risk of NTD's in the target

population. One of these comments urged the agency to revise its

proposal and require fortification at levels of at least 210

g/100 g. However, the majority of these comments recommended

that FDA require fortification of folic acid within the range of 250 to

350 g/100 g. In support of their position, these comments

contended that this range was well within limits for safety and should

not mask the effects of vitamin B12 deficiency. One comment

further argued that at a fortification level of 350 g/100 g,

95 percent of persons in the nontarget population would not consume

more than 1 mg per day. One comment recommended 400 g/100 g

for cereal-grain products. This comment argued that fortification of

enriched cereal-grain products should be at the same level as dietary

supplements.

However, supplemental comments submitted by a majority of the

organizations supporting a higher fortification level, stated that

implementing fortification at a level of at least 140 g/100 g

will constitute a critically important step forward for the health of

American children. Some of these comments further stated that

fortification with at least 140 g/100 g will be the most

efficient and cost-effective approach to ensuring that women of

childbearing age consume the level of folic acid recommended to reduce

the risk of having a neural tube defect affected pregnancy.

The agency agrees with the latter comments. As discussed in the

folic acid health claims proposal (58 FR 53254 at 53279), fortification

of cereal-grain products at 140 g/100 g will produce a

significant increase in daily folate intake, even for women who make

food choices from the ``low'' range of the USDA Food Guide Pyramid and

consume only 5 servings/day of cereal-grain products and 1 bowl of

cereal containing a minimum of 100 g of folic acid. From these

sources alone, these women will consume about 320 g of folic

acid. Addition of a serving or two of vegetables, or of a serving of

fruit, will provide them with a folate intake above 500 g/day.

Thus, fortification of cereal-grain products at 140 g/100 g is

an important step in assisting women of childbearing age achieve the

PHS recommendation of consuming 400 g.

However, if cereal-grain products were fortified at 350 g/

100 g, and the dietary choices indicated above were made, a ``low''

consumer would obtain 610 g folic acid daily from these

sources alone. Thus, at a fortification level of 350 g/100 g a

``high'' consumer could reach intakes of folic acid of more than 1 mg/

day from bread, noodle, rice, and pasta products alone. Additional

consumption of breakfast cereals, fruits, vegetables, and a dietary

supplement by ``high'' consumers could result in daily intakes of

folate of about 2.5 mg/day, a level significantly above the safe upper

limit of daily intake of 1 mg.

The comments supporting fortification of enriched cereal-grain

products at levels above 140 g/100 g did not provide any

information to the agency that it had not considered in developing its

proposed rules. Nor did the comments offer alternative fortification

schemes that would allow addition of folic acid to enriched cereal-

grain products at levels exceeding 140 g/100 g yet limit the

daily intake of folate to levels that are within the safe upper limit

of 1 mg/day. Consequently, FDA disagrees with those comments that

suggested that enriched cereal-grain products be fortified at levels of

at least 210 g/100 g. There simply is no evidence in the

record that such a fortification program would keep folate intakes

within the safe upper limit.

Accordingly, as proposed, the agency is requiring the addition of

folic acid to enriched cereal grain products at a fortification level

of 140 g/100 g. FDA concludes that 140 g/100 g is the

maximum level of fortification of enriched cereal-grain products that

would be safe for all groups.

[[Page 8787]]

Nonetheless, as the agency states in the final rule on the use of

folic acid as a food additive, which is published elsewhere in this

issue of the Federal Register, given the nature of the support for

higher folic acid fortification levels in the comments, if evidence

becomes available to support that there is a reasonable certainty of no

harm at folate intakes above 1 mg/day, FDA would be willing to

reconsider the fortification levels that it is adopting and to consider

raising those levels.

11. Other comments opposed fortification at the proposed level of

140 g/100 g on the grounds that it is too high. These comments

asserted that such fortification may increase the risk of consuming

folate at levels in excess of the safe upper limit of 1 mg/day in a

substantial portion of the general population. Some of these comments

suggested that FDA consider the lower fortification level of 70

g/100 g in conjunction with an educational campaign that could

still be effective in reducing the risk of NTD's yet not pose the risk

of daily consumption of folate in excess of 1 mg/day.

In support of their position, some of these comments noted that the

Food and Nutrition Board recommended the fortification of cereal-grain

products at 70 g/100 g to restore folate lost in the milling

of cereal-grain products. Another comment supporting fortification at

the restoration level contended that such action would permit

additional restorations of nonstandardized foods such as breakfast

cereals. One comment from a foreign government questioned FDA's

decision to require folic acid fortification of all enriched cereal-

grain products when the data do not clearly establish the effectiveness

and safety of the proposed intervention program. However, the comment

suggested support of the Food and Nutrition Board's 1974 proposal for

cereal grain fortification, i.e., fortification with folic acid at 70

g/100 g.

In the standards of identity proposal, FDA tentatively concluded

that fortification of cereal-grain products with 140 g/100 g

folic acid was the most appropriate fortification level of the three

levels analyzed to ensure that folate intakes by the target population

would increase. The comments have not persuaded the agency that a

fortification level of 70 g/100 g could be as effective in

assisting women in the target population to achieve the PHS recommended

daily intake of 400 g. In fact, at a fortification level of 70

g/100 g, the estimated daily folate intake by ``low''

consumers among women of childbearing age is not likely to reach the

PHS recommended levels of 400 g/day without changes in their

food selection practices (see Table 4 of 58 FR 53254 at 53292). While

the agency must ensure that the use of folic acid in the food supply is

safe, it must also provide as great an opportunity as is prudent and

rational for all women of childbearing age to increase their intake to

the recommended level. The agency concludes that a level of 140

g/100 g is the most appropriate fortification level for

enriched cereal-grain products because, based on the results of its

estimated daily intakes, fortification at this level will provide daily

intakes for the nontarget population that remain within the recommended

safe upper limit of 1 mg/day, while providing increased intakes of

folate for women in their childbearing years (see Table 7 of 58 FR

53254 at 53295).

The agency notes, however, that it has reconsidered its proposed

fortification level for breakfast cereals. As fully discussed in the

food additives final rule, published elsewhere in this issue of the

Federal Register, FDA is permitting breakfast cereals to contain up to

400 g of folic acid per serving. As explained in that

document, the estimates for total daily folate intake that FDA

presented in the folic acid health claims proposal were based on the

assumption that all breakfast cereals were fortified at 400 g/

serving. Based on those estimates, daily folate intake for certain

groups in the nontarget population could exceed the recommended safe

upper limit of 1 mg/day. Currently, however, only about 3 to 6 percent

of breakfast cereals fortify at 400 g/serving. The agency has

found no reason to expect that this percentage will change and,

therefore, considers it unlikely that daily folate intake in the

nontarget population will exceed 1 mg with the fortification program

adopted in this final rule and in the food additives final rule.

D. Optional Versus Mandatory

Because of the increased health risk to persons with vitamin B

12 deficiency caused by increased levels of folate intake, FDA

solicited comments in the standards of identity proposal on whether the

addition of folic acid to enriched cereal-grain products should be

required as proposed or made optional.

12. A few comments fully supported the agency's proposal to require

folic acid addition to the enriched cereal-grain products. These

comments contended that required addition of folic acid was an

appropriate means of increasing the daily folate intake of women in the

target population. However, the majority of the comments that responded

to this issue stated that fortification should be voluntary. The

comments cited varied reasons in support of their position. Some

comments stated that the addition of folic acid to enriched cereal-

grain products should be optional pending further evidence that the

benefits outweigh the risk of masking vitamin B12 deficiency.

These comments contended that mandatory fortification of a wide variety

of common products may create difficulty for people wishing to avoid

folic acid. Furthermore, the comments asserted that FDA failed to

establish why mandatory fortification would be necessary given that

under current regulations voluntary fortification of standardized foods

with folic acid is prohibited.

Other comments recommended optional fortification so that millers

will not have to change their enrichment premixes for the general flour

supply, thereby minimizing the costs associated with fortification,

i.e., label changes, analytical testing, and inventory and supply

coordination, especially for products exported to countries that do not

permit folic acid fortification. The comments also stated that

voluntary fortification would facilitate compliance with the various

State enrichment laws.

A few comments opposed to mandatory fortification stated that FDA

failed to offer information as to why voluntary fortification would not

be sufficient to accomplish the public health goal of decreasing the

incidence of pregnancies with neural tube birth defects. The comments

urged FDA to establish a voluntary fortification program for enriched

cereal-grain products and to reassess the need for a mandatory

fortification in several years. One of these comments acknowledged,

however, that it is difficult to predict the extent of voluntary

fortification.

A small number of comments supported voluntary fortification for

only the enriched noodle and macaroni products. The comments contended

that voluntary compliance is consistent with FDA's current standards of

identity for enriched noodle and macaroni products with regard to

vitamin D, calcium, and wheat germ.

The agency does not agree with the comments that argued that the

fortification of enriched cereal-grain products should be voluntary. In

accepting the PHS' and Folic Acid Subcommittee's recommendation to

include fortification as part of an overall plan to increase the folate

nutriture of women of childbearing age, FDA has concluded that in order

for a fortification program to be effective,

[[Page 8788]]

fortification must be mandatory for the enriched cereal-grain products.

FDA is concerned that if it made fortification voluntary, and voluntary

fortification were not widespread, there would be only a negligible

increase in the daily folate intake of the target group, and the intent

of this rulemaking would have been defeated. FDA finds that there is a

public health need for women in their childbearing years to have

adequate folate intake, and that the only way that it can ensure that

they will have such an intake is through mandatory fortification.

FDA has traditionally used mandatory fortification to restore

nutrients lost during the processing of cereal grains and thereby to

address the need for reducing the risk of certain vitamin deficiency-

related problems. The comments have not persuaded the agency that the

same basic approach should not be applied in this case, where low

folate intake represents a risk factor for a neural tube defect-

affected pregnancy. USDA consumption data show that 90 percent of women

of childbearing age consume cereal-grain products. Thus, mandatory

fortification of cereal grains will, as stated above, increase folate

intake among the target group, without requiring significant change in

dietary patterns. Consequently, mandatory fortification of enriched

cereal grains will help to ensure that the daily intake among the

target group will reach the PHS recommended level of 400 g.

Voluntary fortification does not offer the same likelihood that folate

intake will result in intakes that approach the PHS recommendation

because the decision to fortify with folic acid will be at the

discretion of individual manufacturers. Therefore, voluntary

fortification will not adequately address the need for increased folate

intake among women of childbearing age.

FDA derived the fortification levels established in this final rule

based in part on a safe upper limit of 1 mg folate/day. The agency has

concluded that mandatory fortification of the enriched cereal-grain

products at the levels provided in this final rule is not likely to

increase the risk of ``masking'' anemia in vitamin B12 deficient

persons. Thus, the fortification program that FDA is adopting will help

to ensure that the amount of folate that people in all groups of the

population can reasonably be expected to consume will not exceed 1 mg/

day. As discussed in the food additives final rule, the agency has

examined the available data on the levels of folate that may mask

anemia of vitamin B12 deficiency and concluded that a daily intake

of up to 1 mg of folate is safe.

In response to concerns raised by millers regarding label changes,

analytical testing, and inventory and supply coordination, FDA

recognizes that manufacturers will need ample time to implement the

changes required by this amendment of the standards of identity. As

discussed below in the effective date section, FDA is permitting

manufacturers time to coordinate any necessary changes that need to be

made throughout the chain of food production to comply with the

requirements established in this final rule as well as with the

requirements set out in part 101 (21 CFR part 101).

The agency notes that manufacturers will continue to have the

option of using unenriched cereal-grain products as ingredients in

foods and to add enrichment nutrients to those products as they choose.

Several comments from industry representatives raised a concern that

the provisions in the food additive proposal would not permit addition

of folic acid at the bakery site. To the contrary, as discussed in the

food additives final rule, FDA will permit addition of folic acid at

the bakery site as long as it is in compliance with the governing

standard of identity. Consequently, manufacturers will have the same

option of adding folic acid as they have with other enrichment

nutrients when preparing foods that are made with unenriched cereal-

grain ingredients. The agency notes, however, that any products

marketed as a standardized enriched cereal-grain product will have to

contain folic acid at the levels established in this final rule, and

that these requirements preempt state enrichment requirements that are

not identical (see section 403(a) of the act (21 U.S.C. 343(a))).

With regard to exported products, the agency recognizes that

manufacturers may be required to maintain separate inventories for

foreign and domestic sales. While FDA recognizes the importance of

reducing trade barriers, its first obligation is to protect and promote

the health of U.S. consumers. In that regard, the agency concludes

that, because the fortification program adopted in this final rule is

necessary to significantly reduce the incidence of neural tube defect

affected pregnancies, it would not constitute an illegal trade barrier.

E. Other Issues

13. One comment from a consumer interest group recommended that if

research and monitoring does not establish in the next 2 years that the

risk of increasing folate intakes is significant for persons affected

with vitamin B12 deficiency or any folate-related diseases, then

FDA should increase the fortification levels in grain products or other

foods and require that upper safe limits be disclosed in higher dose

products. This comment urged FDA to initiate a rulemaking to restore

refined grain products with most of the vitamins and minerals that are

removed during milling as recommended by the Food and Nutrition Board

in 1974. The comment stated its belief that such an approach would

raise few safety concerns and would not be costly because manufacturers

are already equipped to add nutrients to food.

FDA cannot at this time commit to increasing the levels of folic

acid that may be added to food within the next several years. However,

as stated above, should data become available that demonstrate that

modifications need to be made to improve the effectiveness of the

intervention program, and evidence be developed that the safe upper

limit can be raised, FDA will decide what action is necessary. The

agency notes, however, that the action it is taking in this rulemaking

will more than compensate for the amount of folate lost during the

milling process.

As for the comment's request that FDA initiate rulemaking to

restore to refined grain products other vitamins and minerals that are

removed during milling raises, the agency notes that the request issues

outside the scope of this rulemaking. Therefore, no action on this

request is appropriate at this time.

14. Several comments raised concern regarding the impact of the

proposed regulation on foreign trade. One comment from a foreign trade

association urged FDA to delay finalizing the proposed regulation to

provide the International Harmonization Working Groups the opportunity

to review the proposal and recommend a strategy that would serve public

health goals, while achieving the spirit and intent of the North

American Free Trade Agreement (NAFTA). Another comment stated that the

extra costs and inherent inefficiencies of separate production runs

could preclude some manufacturers from the export marketplace.

Other comments stated that the lack of consistent requirements for

folic acid fortification between major trading partners, e.g., the

United States and Canada, would create problems in cross-border trade

and could result in higher costs for both U.S. and foreign consumers.

Furthermore, these comments asserted that inconsistent requirements

could reduce the competitiveness of domestic

[[Page 8789]]

manufacturers who export their products. Thus, the comments urged FDA

to resolve the issue of exporting folic acid enriched products to

foreign countries by working with foreign governments to permit export

of folic acid-enriched food.

FDA recognizes that the provisions it is adopting in this final

rule may be inconsistent with the fortification policies of other

countries. However, as discussed above, the agency finds that the

action that it is taking in this final rule is necessary to adequately

protect the public health of U.S. consumers. FDA will continue to work

with officials in other countries, particularly parties to NAFTA, to

find ways to reduce barriers to cross-border trading of cereal-grain

products and other foods.

F. Specific Standards of Identity

In this document, the agency is providing for the addition of folic

acid at the level of 140 g/100 g to the individual enriched

cereal-grain products that are the subject of standards of identity.

The agency described indepth the method that it used in arriving at the

levels of addition for folic acid in the specific standards of identity

in the standards of identity proposal. FDA will not describe that

method again in this document except to the extent that clarification

is warranted in response to specific comments. For a complete

discussion of the basis on which FDA established the enrichment levels

for the subject standards of identity, the agency refers interested

persons to the standards of identity proposal (58 FR 53305 at 53307 to

53309).

1. Bakery and Wheat Flour Products

15. One comment, while supportive of the proposal to fortify

cereal-grain products, suggested that a range of levels be permitted

for addition of folic acid to all enriched cereal-grain products

because of the inherent variation in the addition of the vitamins, the

distribution of the vitamins in a food, and the analytical methodology.

The comment suggested that FDA permit the addition of folic acid within

a range of 24 to 35 percent over the amount established for each

individual standard. For example, the comment suggested that the

proposed amount of 0.7 mg/lb for enriched flour should be revised to

0.7 to 0.91 mg/lb. The comment argued that this scheme is the same as

that used for enrichment in the macaroni and noodle standards and is

needed for the same reasons that it is provided for in those standards.

FDA does not agree that it is necessary to provide for a range in

the level of folic acid used in the production of all enriched cereal-

grain products. Providing for a single level, with provision for

reasonable overages within the limits of current good manufacturing

practice (CGMP), has worked well with the other nutrients (thiamin,

niacin, riboflavin, and iron) required to be added to enrich bread,

rolls, and buns and various flour products. The provision for

``reasonable overages'' in the standards for enriched bread, rolls, and

buns (Sec. 136.115(a)(3)) and enriched flour (Sec. 137.165(c)) provides

manufacturers with flexibility to ensure that required levels for the

added nutrients will be met, and that these levels will be maintained

throughout the shelf life of the food under customary conditions of

distribution and storage. While FDA is not establishing a specific

upper limit for folic acid addition, the agency advises that reasonable

variations for overages of folic acid will be assessed on the same

basis as that for the other added nutrients in these foods. Those

reasonable variations are based on a number of factors, including the

technology of nutrient addition, the possibility of nutrient

deterioration, the firms' quality control procedures, and appreciation

by the manufacturer of these factors.

FDA acknowledges that some of the standards for enriched cereal-

grain products that are the subject of this final rule specify the

levels of added nutrient (thiamin, riboflavin, and iron) in terms of

ranges, and FDA has continued this approach with respect to the

addition of folic acid in those products. In addition, the agency notes

that it received a petition (Docket No. 94P-0413/CP 1) subsequent to

the issuance of the folic acid health claims proposal to amend the

standards for enriched macaroni and noodle products to provide for

nutrient addition in terms of a single level with provision for

reasonable overages. However, FDA is not making the change to a single

enrichment level in those standards at this time because, while it has

reached a final decision on folic acid fortification, it has not had an

opportunity to fully analyze the petition. FDA is not aware of any

reason why it should delay action in the present rulemaking while it

analyzes the petition. Thus, until such time as the agency rules on the

petition, the standards in question will continue to provide for

nutrient addition in terms of ranges.

The ranges established in those standards provide a measure of

flexibility in selecting the target level when nutrients are added to

foods that consist of large particles such as farina or rice, or for

preparations (e.g., semolina or other ingredients) used for

manufacturing enriched macaroni or noodle products. The nutrients,

which usually are in the form of a fine powder, have a tendency to

settle out and to make uniform blends with the cereal grains more

difficult to achieve. In such instances, manufacturers, depending on

their application process, may select target levels at the upper end of

the range to ensure that the minimum levels established for the

nutrients will be met. Thus, to enable manufacturers to adhere to

procedures that will deliver the minimum level of nutrients required by

the standards and to compensate for variables in the processing

operations, the agency is continuing to provide for nutrient additions

in terms of ranges for the other enriched foods as set forth below.

FDA also notes that the regulations for nutrition labeling in

Sec. 101.9(g)(4)(i) require that added nutrients be present in the food

at levels that are at least equal to the amount declared on the label.

In addition, Sec. 101.9(g)(6) provides for reasonable overages within

the limits of CGMP. Thus, the manufacturer bears the responsibility of

ensuring that not only will the requirements for added nutrients in the

respective standards of identity be met, but also that the content of

any added nutrient is accurately declared in nutrition labeling.

Therefore, consumers should receive the stated quantity of each added

nutrient whether the standard provides for the added nutrient in terms

of a single level or a range.

a. Enriched flour. No specific comments were received on the

fortification of enriched flour with folic acid. Thus, as proposed, FDA

is requiring that enriched flour contain 0.7 mg/lb of folic acid. FDA

derived this value by adding the fortification level of 0.635 mg/lb to

the Food and Nutrition Board's folate value of unfortified flour of

0.076 mg/lb, which yields 0.711 mg/lb. The agency rounded this value to

0.7 mg/lb. Accordingly, based on this calculation, FDA is amending the

standards of identity for enriched flour (Sec. 137.165) and enriched

self-rising flour (Sec. 137.185), and, by cross-reference, enriched

bromated flour (Sec. 137.160), to require that these foods contain 0.7

mg/lb of folic acid.

b. Enriched bread, rolls, and buns. FDA is amending the standards

of identity for enriched bread, rolls, and buns in Sec. 136.115 to

require that these foods contain 0.43 mg/lb of folic acid. This rate of

fortification is proportionally consistent with the fortification rate

for the B vitamins (thiamin, riboflavin, and niacin) when

[[Page 8790]]

enriched flour is used in making these foods. For example, the levels

of thiamin, riboflavin, and niacin in enriched flour (Sec. 137.165) are

2.9, 1.8, and 24.0 mg/lb, respectively, and in enriched bread

(Sec. 136.115) are 1.8, 1.1, and 15.0 mg/lb, resulting in a ratio of

approximately 1.62 to 1. In the case of the level of folic acid, the

level for enriched flour is 0.7 mg/lb compared to 0.43 mg/lb for bread,

resulting in a ratio 1.63 to 1. The levels of enrichment specified for

the B vitamins and folic acid content are slightly lower in enriched

bread products than in enriched flour to allow the bread products to be

made from the standardized enriched flour without further

fortification.

c. Enriched farina. In the standards of identity proposal, FDA

proposed to establish a fortification level for folic acid in enriched

farina (Sec. 137.305) on the same basis as that for enriched wheat

flour, i.e., 1 lb of the food would contain not less than 0.7 mg of

folic acid.

One comment disagreed with the agency's rationale and argued that

enriched farina is a different product than enriched wheat flour and

therefore should not be fortified at the same level as enriched wheat

flour. The comment asserted that farina is used differently than flour.

For example, according to the comment, farina is often used as an

ingredient in the less expensive pastas to replace the more expensive

semolina. The comment pointed out that farina is also eaten as a hot

cereal, and that precooked breakfast cereals are fortified with folic

acid. The comment did not offer an alternative fortification level or

data on which an alternative level could be based.

Because both wheat flour and farina are made from the endosperm of

wheat, that portion of the wheat kernel that remains after the bran

layer and germ have been removed, and because it is the bran layer and

germ that contain most of the B vitamins, including the naturally

occurring folate, the amount of B vitamins lost during processing would

be similar in both foods. Therefore, the agency finds that it is

reasonable to fortify both flour and farina on the same basic level of

140 g/100 g.

However, FDA acknowledges that enriched farina and enriched flour

may serve different functions. Farina is often used as a substitute for

a flour-containing food, e.g., as a hot cereal at breakfast, with or

without other cereal-grain products being consumed at that meal, and it

may be used in other foods such as pasta. However, the agency finds no

basis to change the fortification level based on these possible end

uses of the products because these uses are governed by other

regulations. For example, when farina is used as an ingredient in the

manufacture of precooked or instant breakfast cereal products, the

level of enrichment is governed by the food additive regulation in

Sec. 172.345. That regulation provides that such ready-to-eat cereals

may be enriched with folic acid up to 100 percent of the daily value

per serving (i.e., 400 g/serving). Neither this final rule nor

the food additive final rule published elsewhere in this issue of the

Federal Register, would affect the continued addition of folic acid to

the precooked or ready-to-eat breakfast cereals that are manufactured

with farina.

With respect to pasta products, the agency notes that the standard

of identity for enriched macaroni and noodle products provides for the

use of farina as an ingredient. However, the agency is not persuaded

that it should adjust the fortification level for farina based on this

possible use of this food. In cases where farina is used as an

ingredient in an enriched macaroni or noodle product, the manufacturer

has the option of adding enrichment nutrients to the farina at the

flour mill or at the manufacturing facility to meet the requirements of

the standard of identity for enriched macaroni or noodle products.

One comment pointed out that farina is not washed before cooking as

had been noted in the proposal, and, thus, washing should not be a

factor in determining appropriate fortification levels.

The agency acknowledges that current farina product labels do not

suggest that enriched farina products need to be rinsed before cooking.

Thus, with current technology, rinsing of the enriched farina product

would not be a factor in deciding on an appropriate value for vitamin

and mineral addition to farina. However, the agency notes that the

proposed upper limit was not based solely on the fact that the product

may be rinsed but also on the fact that it may be diluted when prepared

in other recipes. The comment did not offer data to persuade the agency

to deviate from the proposed upper limit of folic acid addition. Thus,

as proposed, the agency is amending the standard of identity for

enriched farina to provide for an upper limit for folic acid addition

(0.87 mg/lb) that is approximately 25 percent higher than the minimum

of 0.7 mg/lb as it has done for the other B vitamins (thiamin,

riboflavin, and niacin) that are required to be present in enriched

farina.

2. Corn and Rice Products

a. Enriched corn grits. No specific comments were received

regarding the addition of folic acid to enriched corn grits. Thus, as

proposed, FDA is amending Sec. 137.235 to require fortification of

enriched corn grits with the same level of folic acid as that

established for enriched wheat flour products, such that each pound of

the food would contain at least 0.7 mg of folic acid. FDA is also

establishing the proposed upper limit for folic acid fortification of

1.0 mg/lb, which is approximately 50 percent higher than the minimum of

0.7 mg/lb, as it has done for the other B vitamins (thiamin,

riboflavin, and niacin) that are required to be present in enriched

corn grits.

The agency notes that it published a proposed rule in the Federal

Register of October 13, 1995 (60 FR 53480), that would revoke the

standard of identity for enriched corn grits. If comments to the

proposal support revocation of this standard of identity, the

provisions set forth in this final rule for enriched corn grits will

also be revoked. FDA believes, however, that enriched corn grits is a

widely consumed food that is likely to be eaten by women in need of

additional sources of folate. Therefore, should FDA revoke this

standard of identity, the agency is prepared to amend Sec. 172.345, the

food additive regulation on folic acid, to include fortified grits to

the list of nonstandardized foods to which folic acid may be added.

b. Enriched corn meals. No specific comments were received

regarding the enrichment of corn meal products with folic acid. Thus,

as proposed, FDA is amending the standard of identity in Sec. 137.260

to provide for a minimum folic acid level that is consistent with that

established for enriched flour, such that each pound of the food

contains 0.7 mg. Because corn meal products may be used as substitutes

for wheat flour products, the agency believes, as discussed in the

standards of identity proposal (58 FR 53305 at 53308), that consumers

expect to be able to obtain the same levels of nutrients from enriched

corn meals as from enriched wheat flour. FDA is also establishing an

upper limit for folic acid addition (i.e., 1.0 mg/lb which is

approximately 50 percent higher than the minimum fortification level),

as has been done for the added B vitamins. The upper limit on the other

B vitamins is intended to prohibit addition of excessive amounts of the

nutrient and to ensure uniformity in composition of corn meals. FDA

finds that, for the same reasons, an upper

[[Page 8791]]

limit on the addition of folic acid of 1.0 mg/lb is necessary.

c. Enriched rice. The folic acid content of rice varies from 0.008

mg/100 g (0.036 mg/lb) for white rice to 0.020 mg/100 g (0.090 mg/lb)

for brown rice (Ref. 7). FDA proposed to amend the standard of identity

for enriched rice to provide for the addition of not less than 0.7 mg

and not more than 1.4 mg of folic acid per pound (58 FR 53305 at

53312). The agency also noted in the standards of identity proposal

that rice in the United States may be enriched by addition of a powder

mixture containing the added nutrients or by use of a rice premix

consisting of rice kernels coated with a concentrated nutrient mix.

When the powder enrichment procedure is used, the label of the package

generally bears a statement that the rice should not be rinsed before

or drained after cooking, in accordance with Sec. 137.350(c), to ensure

that the rice retains the added nutrients. However, the agency stated,

there is no assurance that these instructions are being followed. In

the case of the rice premix, a special coating is applied to the rice

kernels, so that the added nutrients will not be washed off if the

product is rinsed before cooking. Rice coated with the premix is

blended with unenriched rice such that the finished enriched rice

product will contain the required minimum levels of added nutrients.

The agency stated that the proposed range would provide flexibility in

the production of the enriched rice and ensure that the food, when

prepared for consumption, will contain the required minimum levels of

nutrients.

16. According to comments on the standards of identity proposal,

most enriched rice produced in this country is manufactured using the

powder procedure to add nutrients. A comment stated that some rice

processors are very concerned about the addition of an enrichment

powder mix containing folic acid because folic acid could result in off

colors, taste, and aromas in the enriched rice. The comment maintained

that firms fear that consumers may reject the enriched rice product if

it does not possess the usual white color. It further stated that

processors needed additional time to conduct research on the addition

of folic acid to rice.

While FDA acknowledges that the provision in the enriched rice

standard for the addition of riboflavin has been stayed because of

objections from the industry stating that riboflavin addition results

in a yellow discoloration being imparted to the rice that is

unacceptable to consumers (23 FR 1170, February 25, 1958), the agency

has not received any information from rice processors that demonstrates

that addition of folic acid to rice will result in off colors, taste,

or aromas in the enriched rice product. Thus, as proposed, the agency

is amending the standard of identity for enriched rice (Sec. 137.350)

to include a range for the folic acid fortification level, 0.7 mg/lb to

1.4 mg/lb, with the lower limit being consistent with the folic acid

fortification level for enriched wheat flour. FDA concludes that use of

the same minimum level of fortification is appropriate because it is

consistent with the Food and Nutrition Board's recommendation that the

same restoration level be used for wheat flour, corn products, and rice

(although the Food and Nutrition Board only recommended addition at

restoration levels). FDA is also establishing an upper limit for folic

acid fortification of enriched rice of 1.4 mg/lb, as it has done with

other enrichment nutrients added to rice. As discussed in the standards

of identity proposal (58 FR 53305 at 53309), the upper level is based

on the way that rice is fortified in this country.

The agency recognizes that manufacturers will need time to

experiment with the addition of folic acid to their products. FDA is

providing approximately 2 years from the publication date of this final

rule to allow manufacturers to test their ability to comply with the

new requirements and to make appropriate label changes.

17. One comment stated that, because the powder-enriched rice

suffers substantial nutrient loss when it is washed (as rice is by many

consumers), it is unlikely that folate intakes will increase as much as

FDA estimates. The comment suggested that the agency should,

consequently, increase the fortification level.

FDA disagrees with the comment. For those consumers who wish to

consume ``enriched'' rice, the agency has provided requirements in the

standard of identity for enriched rice to ensure delivery of the

required nutrients. Section 137.350(c) requires that enrichment

nutrients be present in the rice in such form and at such levels that

if the enriched rice is washed, it contains not less than 85 percent of

the minimum quantities of the nutrients required to be present in the

enriched rice. If they are not present in such form or at such levels

to comply with these minimum requirements, the label of the enriched

rice must bear the statement ``to retain vitamins do not rinse before

or drain after cooking'' immediately following the name of the food. In

addition, the label cannot bear cooking directions that call for

washing or draining the enriched rice. In the case of precooked

enriched rice, the package must be labeled with directions for

preparation that, if followed, will avoid washing away or draining off

enrichment ingredients.

As discussed above, FDA is providing for addition of folic acid at

the level of 140 g/100 g of the enriched cereal-grain

products. The agency has concluded that this fortification level is

necessary to help ensure that the total consumption level will not

exceed the recommended daily consumption level of 1 mg (or 1,000

g). To minimize the potential losses in enrichment nutrients

in rice, the agency had provided for a range in the levels, with an

upper limit that is twice that of the minimum level required to be

present in the rice. Thus, rice processors who use the powder-

enrichment procedure, where nutrient losses would be expected to be

greater, will be able to use a level of enrichment nutrients that makes

it likely that consumers will receive the minimum levels of nutrients

required to be in the food.

3. Macaroni and Noodle Products

The standards of identity for enriched macaroni products

(Sec. 139.115), enriched nonfat milk macaroni products (Sec. 139.122),

and enriched noodle products (Sec. 139.155), and the cross- referenced

standards of identity for enriched vegetable macaroni products

(Sec. 139.135) and enriched vegetable noodle products (Sec. 139.165),

provide for significantly higher levels of nutrient addition than the

related flour standards of identity because these products are usually

cooked in a large amount of water that is usually discarded after

cooking and before consumption of the macaroni and noodle products.

18. One comment asserted that because of the preparation process

for macaroni and noodle products, vitamin retention data are absolutely

essential before any level of enrichment can be discussed. Thus, the

comment recommended that FDA delay implementation of folic acid

fortification of cereal-grain products until more concrete information

is available on vitamin retention with cooking.

FDA is not delaying the implementation of folic acid fortification,

as suggested by the comment, because of the need to increase the folic

acid levels in the diets of women of childbearing age. The agency

recognizes that there will be losses in the content of water soluble

vitamins when the enriched macaroni and enriched noodle products are

cooked in water, and that water is drained from the foods before

consumption (Ref. 8). The agency also

[[Page 8792]]

acknowledges that data on retention of the vitamins (thiamin, niacin,

and riboflavin) required to be added to enrich these foods are limited,

and that it is difficult to make inferences as to the retention of

added folic acid when folic acid enriched products are cooked in water,

and the water is discarded. However, there are some data to suggest

that the retention rates are similar.

According to a study conducted by Ranhortra, et al. (Ref. 8), on

the retention rates of the thiamin, niacin, and riboflavin in three

enriched pasta products (spaghetti, noodles, and macaroni), at least 50

percent (75 to 77 percent on average) of the added nutrients was

retained after cooking in water and draining. This study looked at the

retention of the naturally occurring folate in the pasta products,

before and after cooking, and found that the retention rate was 77 to

79 percent. Based on this data, FDA does not expect that the retention

rate of folic acid in these products would be significantly different

from the retention rates of the other B vitamins.

FDA recognizes that, as with other grain products, manufacturers

will need to conduct research on the most effective means of adding

folic acid and of ensuring that the added folic acid will be available

in the finished food. Such studies will need to focus on not only the

method of adding the nutrient but also on the stability of the vitamin

during usual conditions of distribution and storage. The agency notes

that similar studies were required when FDA established requirements

for the addition of the other B vitamins to enriched cereal-grain

products. In addition to studies, it may be necessary for manufacturers

to develop label instructions on how the product should be prepared,

e.g., instructions on limiting the amount of water to be used in its

preparation or cooking time, and on whether the cooked food can be

rinsed without loss of nutrients before serving, to ensure maximum

retention of folic acid and the added water soluble nutrients.

FDA is requiring the addition of folic acid to macaroni and noodle

products in the same proportion as it is requiring such addition to

enriched flour, except that the required level (expressed in terms of a

range) will be approximately 25 percent higher for macaroni and noodle

products than the required level of folic acid that is to be added to

flour. This 25-percent increment is consistent with the requirements

for the other added nutrients (thiamin, riboflavin, niacin, and iron)

in the enriched macaroni and noodle products standards, compared to

those in the standards of identity for flour products.

Accordingly, as proposed, FDA is requiring that the enriched

macaroni and noodle products contain from 0.9 to 1.2 mg/lb of folic

acid.

G. Effective Date

19. Many comments expressed concern over the statement in the

standards of identity proposal that the final rule would become

effective 1 year after publication. The comments stated that it would

be difficult and impractical to synchronize the addition to a food of a

folic acid-fortified enriched cereal- grain product with the

availability of revised labels for that food that declare folic acid in

the ingredient statement. These comments pointed out that enrichment

nutrients are generally not added to each separately labeled product

but are added to thousands of pounds of flour at the flour mill, the

flour is sold to other manufacturers as an ingredient, and then this

ingredient is used in many different products. Thus, the comments

asserted that as a matter of economic necessity, the enrichment of all

these products occurs at the same time, regardless of the availability

of new labeling. One comment recommended that FDA establish an

effective date of at least 2 years from the date of publication of the

final rule. The comment asserted that a 2-year period would allow

adequate time to incorporate changes on labels of slower moving

products as well as products with higher retail turn rates. Thus, the

comment continued, existing packaging inventory could be used, thereby

reducing the cost impact of the regulation. Another comment suggested a

``phase-in'' period of at least 3 years or, in the alternative, an

effective date consistent with the next uniform effective date,

whichever is later. In support of the suggestion, the comment asserted

that a ``phase-in'' period would allow label changes to take place

concurrent with the folic acid addition on a product-by-product basis.

In addition, the comment contended, such action would allow

manufacturers to exhaust their current label inventory and reduce the

economic impact of the regulation. Moreover, the comment continued,

additional time is needed for analytical testing for declaration of

folic acid in nutrition labeling.

FDA acknowledges the concerns raised in these comments regarding

label changes that must accompany the addition of folic acid to

enriched cereal-grain products and to foods in which these products are

used as ingredients. FDA is persuaded by the concerns raised in the

comments to establish an effective date that will provide manufacturers

with time to implement the label and formulation changes required by

the amendments established in this final rule. The agency agrees with

the comment that suggested that FDA establish an effective date of at

least 2 years from the date of publication of the final rule. A 2-year

period would allow manufacturers time to exhaust current packaging

inventory, add folic acid to their statement of ingredients and the

nutrition facts panel as other changes are made to update package

labeling, and subsequently ensure that packaging is available that

accurately reflects the addition of folic acid to their products.

Furthermore, the agency points out that a 2-year period is consistent

with the amount of time given for implementation of the Nutrition

Labeling and Education Act (NLEA) requirements. Thus, the effective

date of this final rule will be January 1, 1998. The agency notes,

however, that compliance with the requirements established in this

final rule may begin immediately, provided that the label accurately

reflects that folic acid has been added to the product. Furthermore,

the agency will not object to the use of stickers to bring a product

label into compliance with the ingredient labeling and nutrition

labeling provisions. The agency notes, however, that unless the

standardized food bears a claim about folate, the declaration of folate

in the nutrition label is voluntary.

20. A few comments that raised concern about label changes that

must accompany the addition of folic acid suggested that the agency

permit folic acid to be added to the product without requiring

declaration in the ingredient statement. One comment contended that

there was no safety issue regarding folic acid that would require its

declaration on the label.

Traditionally, the agency has not permitted manufacturers who

change their formulas by adding or deleting ingredients to use

noncompliant labels. Furthermore, as discussed in response to the

previous comment, the agency is establishing an effective date in this

final rule that will provide industry ample time to ensure that

products enriched with folic acid are labeled in compliance with the

regulations.

In response to the argument that the addition of folic acid need

not be declared because it does not raise a safety issue, the agency

advises that the act requires that all foods fabricated from two or

more ingredients declare each of its ingredients by common or usual

name in a list of ingredients. This

[[Page 8793]]

requirement applies without regard to whether there is a safety issue

regarding the food. Consequently, the agency has not been persuaded by

the comments to permit the addition of folic acid to foods without also

requiring that folic acid be declared in ingredient labeling.

III. Economic Impact

FDA has examined the impacts of this final rule to require the

addition of folic acid to enriched cereal-grain products that conform

to a standard of identity as required by Executive Order 12866 and the

Regulatory Flexibility Act. Executive Order 12866 directs agencies to

assess all costs and benefits of available regulatory alternatives and,

when regulation is necessary, to select regulatory approaches that

maximize net benefits (including potential economic, environmental,

public health and safety, and other advantages; distributive impacts;

and equity). The Regulatory Flexibility Act (Pub. L. 96-654) requires

the analysis of options for regulatory relief for small businesses. FDA

finds that this final rule is not a significant regulatory action as

defined by Executive Order 12866. In compliance with the Regulatory

Flexibility Act, the agency certifies that this final rule will not

have a significant impact on a substantial number of small businesses.

On October 14, 1993 (58 FR 53305 at 53309), FDA published an

economic impact analysis of the proposed requirements under the

previous Executive Order (E.O. 12291). In the analysis, the agency

evaluated the following regulatory options:

1. Improve dietary practices among women of childbearing age.

2. Require fortification with folic acid at 140 g/100 g.

3. Require fortification with folic acid at: (a) A lower level,

specifically 70 g/100 g; or (b) a higher level, specifically

350 g/100 g.

In response to the standards of identity proposal, the agency

received several comments that provided information that has altered

its economic impact analysis. Costs and benefits for each of the

regulatory options are examined below.

A. Costs

Cost estimates are revised first for fortification at 140 g/

100 g followed by the cost estimates for fortification at 70

g/100 g and 350 g/100 g.

1. Require Fortification With Folic Acid at 140 g/100 g

Costs of fortifying with folic acid at 140 g/100 g include

health costs and reformulation costs.

a. Health costs. Potential health costs of this regulatory option

include the costs of neurologic disease associated with masking of the

anemia of vitamin B12 deficiency. Several studies have found that

folic acid can mask the anemia of vitamin B12 deficiency at levels

as low as 250 g/day. Although there is no scientific consensus

on the percentage of diagnoses of vitamin B12 deficiency anemia

that would be complicated by folate intake at this level, the agency

has determined that adverse health effects are not significant until

folate intake reaches 1 mg/day. In the proposal, FDA tentatively

concluded that the 140 g/100 g level for fortification of

enriched cereal grain products was the most appropriate level based on

a regulation that would have required that fortification of all

breakfast cereals be limited to 100 g folic acid/serving. This

limitation was proposed under a separate food additive regulation

published elsewhere in the same Federal Register (58 FR 53312). With

this option, 140 g/100 g, FDA preliminarily concluded that

intake of persons in the target and nontarget populations would remain

below 1 mg/day.

Comments submitted in response to the proposal to limit breakfast

cereals to 100 g folic acid/serving persuaded the agency to

allow breakfast cereals to continue to contain up to 400 g

folic acid/serving. If all breakfast cereals were fortified at the

level of 400 g/serving, some high end consumers could consume

more than 1 mg folate/day. However, most cereals currently are

fortified at a level of 100 g/serving (25 percent of the

reference daily intake (RDI)) and only an estimated 5 percent of

breakfast cereals fortify at a level of 400 g (100 percent of

the RDI).

Further, it is unlikely that manufacturers of breakfast cereals

will increase the folic acid level in cereals from 100 g/

serving to 400 g/serving. Since most breakfast cereals that

contain at least 40 g/serving (10 percent of the RDI) of folic

acid can now make health claims (if all other criteria are met),

manufacturers have no incentive to reformulate from 100 g to

400 g per serving and incur reformulation costs.

There are a number of confounding uncertainties that make it

difficult to estimate the potential health costs of folic acid

fortification of enriched grain products (Ref. 9). These include:

1. Current intakes estimated from food consumption survey data may

underestimate actual intakes due to underreporting of food intake;

2. The folate content of foods may be underestimated due to

methodologic difficulties;

3. Good data on the distribution of dietary supplement intake are

not available;

4. Estimates of masking of anemia (with subsequent progression of

neurologic symptoms) based on enumerating only those associated with

pernicious anemia would underestimate potential adverse effects because

all vitamin B12 deficiencies may lead to neurologic problems; and

5. It is difficult to predict effects of changes in dietary

patterns that occur simultaneously with, but independently of, this

regulation. Such changes may be the result of educational efforts by

various organizations, physicians, and health care providers or in

response to health claims.

The last factor is particularly problematic. Recent surveys have

shown a growing awareness of the value of increased folate intake among

both the population as a whole and, specifically, among women of

childbearing age. From 1994 to 1995, awareness of the problems

associated with insufficient folic acid intake grew from 28 to 44

percent among women of all ages (Ref. 10). As awareness grows, it is

likely that folic acid intake will increase in the target group. In

addition, new label claims allowed by the final rule for health claims

on the association between folate intake and a reduced risk of NTD's

are also expected to increase folic acid intake among women of

childbearing age. However, the survey mentioned above also showed that

such awareness is strongly positively correlated with education, so

that these messages may not reach less well- educated women in the

population.

In the folic acid health claims proposal, FDA tentatively found

that there were several nontarget groups whose intake levels of folate

may approach 1 mg/day (intakes > 800 g/day) with a level of

140 g/day and use of dietary supplements. These include

individuals in groups including children 4 through 10 years of age and

males 11 through 18, 19 through 50, and 51+ years of age. Individuals

at risk of pernicious anemia include both males and females over 51 and

Hispanic females ages 40 and above. The largest group at potential risk

includes males over 51 who take dietary supplements. In order to be at

risk of potential adverse effects from consuming greater than 1 mg

folate/day individuals must: (1) Consume an excessive amount of folic

acid through some combination of supplements containing folic acid and

consumption of fortified enriched grain products and other products

containing folic acid; and (2) have low vitamin B12 status or have

vitamin B12 deficiency.

[[Page 8794]]

Because of the difficulties mentioned above, it is not possible to

estimate the number of people in the high risk subgroup who fit all of

these categories.

However, one such attempt has been made between the time of the

standards of identity proposal and this final rule. In this analysis,

Romano et. al. made the following assumptions:

1. The annual incidence of pernicious anemia is 9.5 to 16.7 per

100,000 persons (based on two European population-based studies);

2. With low level fortification, 5 to 10 percent of these patients

would receive enough folic acid to mask the anemia of vitamin B12

deficiency; and

3. Between ``24 and 26 percent of patients with pernicious anemias

whose anemias respond to folic acid develop neurologic signs'' (Ref.

11).

Based on these assumptions, the authors estimated that

approximately 500 people per year would develop neurologic disease as a

result of low level folic acid fortification. Other authors contend

that this estimate may considerably understate the number of cases

(Ref. 12). On the other hand, one uncertainty not acknowledged by this

analysis is that this rule may create a market for cereal-grain

products that are not ``enriched.'' A nonstandardized cereal-grain

product could be produced that was not labeled as being enriched with

folate (although it could have other vitamins and minerals added and be

labeled to reflect this fact) and could be marketed to people at risk

of vitamin B12 deficiency. If such a market developed, and at-risk

persons were encouraged to consume products not enriched with folic

acid, this problem might be reduced. In addition, sale to high risk

subgroups of nonstandardized products such as whole wheat breads

(mentioned earlier in this preamble) which do not need to be enriched,

may increase as a result of this rule.

Another uncertainty that would reduce the number of cases of masked

anemia, mentioned by one comment, is the percentage of cases of

B12 deficiency that could be discovered with routine population

screening. If such tests were performed proactively, B12

deficiencies might be identified before neurologic symptoms developed.

In addition, it is not clear whether the European population-based

studies that reported the annual incidence of diagnosed pernicious

anemia are relevant to the U.S. population. Some population groups in

the United States (e.g., African-American women) appear to experience

an earlier age-at-onset of pernicious anemia than occurs with

pernicious anemia in Northern European countries, which are

predominantly Caucasian populations.

Although not able to estimate an absolute number, FDA has

calculated a cost per case of neurologic symptoms resulting from

masking of the anemia of pernicious anemia so that a break-even point

may be calculated at which point benefits would equal the costs. The

cost-per-illness will be calculated using the sum of medical costs and

the cost of lost utility. The majority of medical costs, which include

costs for physicians, other hospital services, and drugs, are normally

paid by insurance such that estimates based on willingness-to-pay to

avoid death would not be likely to be included. Other utility losses,

including death, pain and suffering, immobility, and lost productivity

associated with morbidity, are calculated as a function of the

willingness- to-pay (WTP) to avoid death. Thus, for example, each day

of morbidity is a day spent in less than perfect health engendering

some utility loss. That is, each day of illnesses is somewhere between

a day of full utility, 1, and death, 0. Because WTP to avoid death does

not include the medical expenditures mentioned above, these costs are

calculated separately.

The expected utility loss estimates were calculated in the

preliminary economic impact analysis (the PRIA) in the standards of

identity proposal. The most common symptoms of a delay in the diagnosis

of vitamin B12 deficiency are permanent paresthesia (numbness or

tingling) in the hands or feet and ataxia (inability to coordinate

voluntary muscular movements).

In the standards of identity proposal, FDA estimated the cost per

case to be approximately $538,000 (Ref. 13). This estimate was

calculated using weighted probabilities of a mild (95 percent) and a

severe case (5 percent) and the value of expected utility loss per case

of neurologic disability. For each state, mild and severe, a health

status value was calculated that related the state to a day of

``perfect health''. Thus, a person with a mild case of neurologic

disability is calculated to enjoy only 70 percent of the utility per

day as that of a person in a perfectly healthy state. For a more severe

case it would be approximately 50 percent (Ref. 14). Using the likely

duration of each illness, the utility loss from a severe neurologic

disability was found to be equivalent to a loss of 5.56 perfect-health

years. From the value of a perfect health year, $138,889 (Ref. 14), the

value of expected utility loss per case of mild neurologic disability

was estimated to be $525,598. The utility loss due to severe neurologic

disability was estimated in a similar fashion to be $772,598 per case.

The weighted value (based on likelihood of a mild versus severe case)

of a case of masked pernicious anemia leading to permanent adverse

health effects was calculated as the weighted mean: (0.95 x 525,598)

+ (0.05 x 772,598) = $537,948.

In addition to utility costs, hospital costs of neurologic effects

due to pernicious anemia have been estimated by Romano et al. (Ref.

11). In this study, each neurologic case requires hospitalization once

for an average duration of 16 days at $867/day. After factoring in

physician services and other direct and indirect costs, the total

direct outlay cost of neurologic disease as a result of folic acid

fortification was estimated to be $33,000 per case (Ref. 11). Total

costs per case are thus calculated to be $570,000.

However, as mentioned in Romano et al., the cost estimate may be

too high because these estimates assume that all neurologic disease

would be severe, and mild cases may not require hospitalization (Ref.

11). In addition, this estimate may be too high if there were routine

population wide screening for vitamin B12 deficiency, although

this is not currently occurring nor is it likely to be instituted. At

the same time, however, the estimate may be too low if a case leads to

later complications or to the need for lifelong skilled nursing care

(Ref. 11).

These costs, lost utility and hospital costs, are not annual costs.

Once someone has experienced permanent adverse health effects from

masked pernicious anemia, that person ought not to be included in the

costs estimated for subsequent years, since the discounted value of

their permanent adverse health effects has already been calculated and

attributed to the first year. Any costs in subsequent years would

involve only those entering the at-risk age pool.

b. Other health costs. FDA is aware of the potential for other

health problems resulting from increased long-term intakes of folic

acid but has no data with which to quantify these costs.

c. Reformulation costs. Reformulation costs associated with this

option were estimated in the proposal to be $27 million for the first

year. The cost of adding the required folic acid is approximately $4

million per year. The cost of testing was estimated to be about $2.5

million per year and the cost of the required label changes $20

million. FDA will use these costs for this final rule as no comments

were received on this part of the analysis.

In addition, some countries, such as Canada, do not allow folic

acid fortification of these products. Thus, this option would require

that separate

[[Page 8795]]

production runs be made for fortified products exported, to and

imported from, these countries. This requirement may preclude some

manufacturers from the export market. None of the comments provided

information that would assist in determining the costs of having

different international requirements.

2. Costs of Requiring Fortification With Folic Acid at Either 70

g/100 g or 350 g/100 g

The total cost of the option to fortify at 70 g/100 g in

the first year was estimated in the proposal to be $25 million plus the

cost of separate production runs for these products exported to and

imported from certain foreign countries. For the option of fortifying

with folic acid at 350 g/100 g, the PRIA estimated a cost of

$1.88 billion annually.

With the latter option, the folate intake of some consumers at risk

of vitamin B12 deficiency (including pernicious anemia) would be

raised to levels exceeding 1 mg per day. One comment to the proposal

said that the estimated health costs of fortifying at this (higher)

level were unrealistically high as FDA had failed to take into account

that each subsequent year should only account for new cases (Ref. 11).

Because of the problems with estimating numbers of people who will

become ill at either level, FDA will not quantify these costs.

Reformulation costs. In the proposal, the cost of the folic acid

required to fortify at 350 g/100 g was estimated to be

approximately $10 million per year. The cost of testing was estimated

to be $2.5 million and the cost of the required label changes was

estimated to be $20 million.

B. Benefits

1. Require Fortification with Folic Acid at 140 g/100 g

The primary benefit of this option is a reduction in the number of

infants born with NTD's each year. In addition, a possible benefit will

be a reduction in cardiovascular diseases from intake of increased

folate. However, there is still tremendous uncertainty with respect to

the latter effect (for a more complete discussion, see folic acid food

additive document published elsewhere in this Federal Register).

Based on a synthesis of information from several studies, including

those which used multivitamins containing folic acid at a daily dose

level of 0.4 mg, it was inferred that folic acid alone at

levels of 0.4 mg per day will reduce the risk of NTD's. This conclusion

was based on two studies, one from a high risk population (Hungary)

with a small number of subjects that was found to be 100 percent

effective and another from a study that showed zero risk reduction in a

low prevalence population (California and Illinois). From these

studies, the PHS estimated a reduction of 50 percent of the number of

NTD's in the United States. Other studies evaluated by PHS varied in

their results. A possible explanation for the lack of effectiveness was

that studies were conducted in populations with a low prevalence of

NTD's which may not have had a folate-related subset of NTD's.

In a study by Shaw et al., the reduction in NTD risk associated

with folate intake is consistent with other studies, but the reduced

risk was found to be specific to particular subsets of the population,

primarily non-Hispanic women and women whose education did not exceed

high school (Ref. 15). For Hispanic women, the risk reduction was

approximately 10 percent. In a study by Romano et. al., the 50 percent

estimate of reduced risk of NTD's was used with literature-based

sensitivity limits of 67 percent (Ref. 16) and 20 percent (Refs. 11 and

17).

In the proposal, FDA estimated that under the 140 g/100 g

option, 116 NTD's per year would be prevented (50 percent reduction).

Initiation of this option was also estimated to prevent an additional

25 infant deaths each year. Total benefits of this option were

estimated to be between $651 and $788 million per year.

There is no consensus on the dose-response relationship between

folate intake and the reduction in risk of NTD's. However, using a

lower bound of 10 percent and an upper bound of a 50 percent reduction

in NTD's, the estimated reductions in total cases would be between 25

(5 deaths) and 125 (27 deaths) resulting in quantified benefits ranging

from $220 to $700 million.

2. Require Fortification with Folic Acid at 70 g/100 g and 350

g/100 g

a. 70 g/100 g. The benefit of requiring fortification of

these products at 70 g/100 g was estimated in the proposal to

be between $326 and $394 million. Using the sensitivity limits

mentioned above, 10 to 50 percent of the estimated benefits would range

from $110 to $346 million.

b. 350 g/100 g. The benefit of requiring fortification of

these products at 350 g/100 g is estimated to be between $550

million and $1.4 billion. This option is the only option that would

generate significant health costs.

C. Conclusion

In accordance with Executive Order 12866, the agency has analyzed

the economic effects of this final rule and has determined that this

rule, if issued, will not be an economically significant rule as

defined by that order.

The cost of this final rule in the first year is estimated to be

approximately $27 million which includes the cost of relabeling,

testing, and fortification. In addition, there may be some health costs

associated with neurologic symptoms resulting from masking the anemia

of vitamin B12 deficiency as well as the cost of separate

production runs for products exported to and imported from certain

foreign countries. The cost of the proposed action in each year after

the first year should be approximately 25 percent of the first year

cost. The benefits are estimated to be between $220 and $700 million

per year. Using a value of $570,000 per case of masked pernicious

anemia resulting in neurologic damage, the break-even number of these

cases at which costs would equal benefits would fall between 386 and

1,228.

Although reformulation costs of this option are approximately $27

million, the cost per firm is expected to be very small. Therefore, in

accordance with the Regulatory Flexibility Act, FDA has determined that

this rule will not have an adverse impact on a substantial number of

small businesses.

IV. Environmental Impact

The agency has carefully considered the potential environmental

effects of this action. FDA has concluded that the action will not have

a significant impact on the human environment, and that an

environmental impact statement is not required. The agency's finding of

no significant impact and the evidence supporting that finding,

contained in an environmental assessment, may be seen in the Dockets

Management Branch (address above) between 9 a.m. and 4 p.m., Monday

through Friday.

V. References

The following references have been placed on display in the Dockets

Management Branch (address above) and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday through Friday.

1. Centers for Disease Control and Prevention, ``Recommendations

for the Use of Folic Acid to Reduce the Number of Cases of Spina

Bifida and Other Neural Tube Defects,'' in Morbidity and Mortality

Weekly Reports, 41, 1-7, 1992.

2. USDA, Nationwide Food Consumption Survey/Individual Intake-

1987-1988, accession no. PB90-504044, National

[[Page 8796]]

Technical Information Service, Springfield, VA, 1990.

3. Food and Nutrition Board, National Research Council, National

Academy of Sciences, Proposed Fortification Policy for Cereal-Grain

Products, Washington, DC, 36 pp., 1974.

4. Nationwide Food Consumption Survey, Continuing Survey of Food

Intakes by Individuals: Women 19-50 Years Old and Their Children 1-5

years, 1 day, 1985; United States Department of Agriculture,

Hyattsville, MD; NFCS, CSFII, Report No. 85-1, 1985.

5. Subcommittee on Food Technology, Committee on Food

Protection, Food and Nutrition Board, National Research Council,

National Academy of Sciences, Proceedings of a Workshop on

Technology of Fortification of Cereal-Grain Products, Washington,

DC, May 16-17, 1977.

6. USDA Handbook 8-20: Composition of Foods, Cereal Grains, and

Pasta, Raw Processed, Prepared. Rev., October 1989.

7. Hoffpauer, D.W., ``Rice Enrichment for Today,'' Cereal Foods

World, vol. 37, No. 10, pp. 757-759, 1992.

8. Ranhortra, G.S., J.A. Gelroth, F.A. Novak, and R.H. Matthews,

``Retention of Selected B Vitamins in Cooked Pasta Products,''

Cereal Chemistry, vol. 60, No. 6, pp. 476-477, 1985.

9. Crane, N. et al., ``Evaluating Food Fortification Options:

General Principles Revisited with Folic Acid,'' American Journal of

Public Health, vol. 85, No. 5, pp. 660- 666, 1995.

10. FDA, Health and Diet Survey, 1994 and 1995.

11. Romano, P.S. et al., ``Folic Acid Fortification of Grain: An

Economic Analysis,'' American Journal of Public Health, vol. 85, No.

5, pp. 667-676, 1995.

12. Perez-Escamilla, R., ``Folic Acid Fortification for the

Prevention of Neural Tube Defects: Consensus Needed on Potential

Adverse Effects,'' American Journal of Public Health, vol. 85, No.

11, pp. 1587-1588, 1995.

13. Healton, E.B., D.G. Savage, J.C. Brust, T.J. Garett, J.

Lindenbaum, ``Neurologic Aspects of Cobalamin Deficiency,''

Medicine, vol. 7, No. 4, pp. 229-245, 1991.

14. Research Triangle Institute, ``Quality of Well-Being Scale

in Estimating the Value of Consumers' Loss from Food Violating the

FD&C Act,'' vol. II, Final Report, 1988.

15. Shaw, G.M. et al., ``Periconceptional Vitamin Use, Dietary

Folate and the Occurrence of Neural Tube Defects,'' Epidemiology

Resources Inc., 1995.

16. MRC Vitamin Study Research Group, ``Prevention of Neural

Tube Birth Defects: Results of the Medical Research Council Vitamin

Study,'' Lancet, vol. 338, pp. 131- 137, 1991.

17. Mills, J.L., G.G. Rhoads, J.L. Simpson, G.C. Cunningham,

M.R. Conley, M.R. Lassman, M.E. Walden, D.R. Depp, H.J. Hoffman,

``The Absence of a Relation Between the Periconceptional Use of

Vitamins and Neural-tube Defects,'' New England Journal of Medicine,

321:430-435, 1989.

List of Subjects

21 CFR Part 136

Bakery products, Food grades and standards.

21 CFR Part 137

Cereals (food), Food grades and standards.

21 CFR Part 139

Food grades and standards.

Therefore, under the Federal Food, Drug, and Cosmetic Act and under

authority delegated to the Commissioner of Food and Drugs and

redelegated to the Director, Center for Food Safety and Applied

Nutrition, 21 CFR parts 136, 137, and 139 are amended as follows:

PART 136--BAKERY PRODUCTS

1. The authority citation for 21 CFR part 136 continues to read as

follows:

Authority: Secs. 201, 401, 403, 409, 701, 721 of the Federal

Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 343, 348, 371,

379e).

2. Section 136.115 is amended by revising paragraph (a)(1) to read

as follows:

Sec. 136.115 Enriched bread, rolls, and buns.

(a) * * *

(1) Each such food contains in each pound 1.8 milligrams of

thiamin, 1.1 milligrams of riboflavin, 15 milligrams of niacin, 0.43

milligrams of folic acid, and 12.5 milligrams of iron.

* * * * *

PART 137--CEREAL FLOURS AND RELATED PRODUCTS

3. The authority citation for 21 CFR part 137 continues to read as

follows:

Authority: Secs. 201, 401, 403, 409, 701, 721 of the Federal

Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 343, 348, 371,

379e).

4. Section 137.165 is amended by revising paragraph (a) to read as

follows:

Sec. 137.165 Enriched flour.

* * * * *

(a) It contains in each pound 2.9 milligrams of thiamin, 1.8

milligrams of riboflavin, 24 milligrams of niacin, 0.7 milligrams of

folic acid, and 20 milligrams of iron.

* * * * *

5. Section 137.185 is amended by revising paragraph (a) to read as

follows:

Sec. 137.185 Enriched self-rising flour.

* * * * *

(a) It contains in each pound 2.9 milligrams of thiamin, 1.8

milligrams of riboflavin, 24 milligrams of niacin, 0.7 milligrams of

folic acid, and 20 milligrams of iron.

* * * * *

6. Section 137.235 is amended by revising paragraph (a)(1) to read

as follows:

Sec. 137.235 Enriched corn grits.

(a) * * *

(1) It contains in each pound not less than 2.0 milligrams (mg) and

not more than 3.0 mg of thiamin, not less than 1.2 mg and not more than

1.8 mg of riboflavin, not less than 16 mg and not more than 24 mg of

niacin or niacinamide, not less than 0.7 mg and not more than 1.0 mg of

folic acid, and not less than 13 mg and not more than 26 mg of iron

(Fe);

* * * * *

7. Section 137.260 is amended by revising paragraph (a)(1) to read

as follows:

Sec. 137.260 Enriched corn meals.

(a) * * *

(1) It contains in each pound not less than 2.0 milligrams (mg) and

not more than 3.0 mg of thiamin, not less than 1.2 mg and not more than

1.8 mg of riboflavin, not less than 16 mg and not more than 24 mg of

niacin or niacinamide, not less than 0.7 mg and not more than 1.0 mg of

folic acid, and not less than 13 mg and not more than 26 mg of iron

(Fe);

* * * * *

8. Section 137.305 is amended by revising paragraph (a)(1) to read

as follows:

Sec. 137.305 Enriched farina.

(a) * * *

(1) It contains in each pound not less than 2.0 milligrams (mg) and

not more than 2.5 mg of thiamin, not less than 1.2 mg and not more than

1.5 mg of riboflavin, not less than 16.0 mg and not more than 20.0 mg

of niacin or niacinamide, not less than 0.7 mg and not more than 0.87

mg of folic acid, and not less than 13.0 mg of iron (Fe).

* * * * *

9. Section 137.350 is amended by revising paragraph (a)(1) to read

as follows:

Sec. 137.350 Enriched rice.

(a) * * *

(1) Not less than 2.0 milligrams (mg) and not more than 4.0 mg of

thiamin, not less than 1.2 mg and not more than 2.4 mg of riboflavin,

not less than 16 mg and not more than 32 mg of niacin or niacinamide,

not less than 0.7 mg and not more than 1.4 mg of folic acid, and not

less than 13 mg and not more than 26 mg of iron (Fe).

* * * * *

[[Page 8797]]

PART 139--MACARONI AND NOODLE PRODUCTS

10. The authority citation for 21 CFR part 139 continues to read as

follows:

Authority: Secs. 201, 401, 403, 409, 701, 721 of the Federal

Food, Drug, and Cosmetic Act (21 U.S.C. 321, 341, 343, 348, 371,

379e).

11. Section 139.115 is amended by revising paragraph (a)(1) to read

as follows:

Sec. 139.115 Enriched macaroni products.

(a) * * *

(1) Each such food contains in each pound not less than 4.0

milligrams (mg) and not more than 5.0 mg of thiamin, not less than 1.7

mg and not more than 2.2 mg of riboflavin, not less than 27 mg and not

more than 34 mg of niacin or niacinamide, not less than 0.9 mg and not

more than 1.2 mg of folic acid, and not less than 13 mg and not more

than 16.5 mg of iron (Fe);

* * * * *

12. Section 139.122 is amended by revising the first sentence of

paragraph (a)(3) to read as follows:

Sec. 139.122 Enriched nonfat milk macaroni products.

(a) * * *

(3) Each such food contains in each pound not less than 4.0

milligrams (mg) and not more than 5.0 mg of thiamin, not less than 1.7

mg and not more than 2.2 mg of riboflavin, not less than 27 mg and not

more than 34 mg of niacin or niacinamide, not less than 0.9 mg and not

more than 1.2 mg of folic acid, and not less than 13 mg and not more

than 16.5 mg of iron (Fe). * * *

* * * * *

13. Section 139.155 is amended by revising paragraph (a)(1) to read

as follows:

Sec. 139.155 Enriched noodle products.

(a) * * *

(1) Each such food contains in each pound not less than 4

milligrams (mg) and not more than 5 mg of thiamin, not less than 1.7 mg

and not more than 2.2 mg of riboflavin, not less than 27 mg and not

more than 34 mg of niacin or niacinamide, not less than 0.9 mg and not

more than 1.2 mg of folic acid, and not less than 13 mg and not more

than 16.5 mg of iron (Fe);

* * * * *

Dated: February 26, 1996.

David A. Kessler,

Commissioner of Food and Drugs.

Donna E. Shalala,

Secretary of Health and Human Services.

[FR Doc. 96-5014 Filed 2-29-96; 12:03 pm]

BILLING CODE 4160-01-P