Lead in Food and Color Additives and GRAS Ingredients; Request for Data

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 73, 74, 168, 172, 173, 182, and 184

[Docket No. 93N-0348]

Lead in Food and Color Additives and GRAS Ingredients; Request

for Data

AGENCY: Food and Drug Administration, HHS.

ACTION: Advance notice of proposed rulemaking.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that it

intends to take several related actions to reduce the amount of lead in

food from the use of food and color additives and food ingredients

whose use is generally recognized as safe (GRAS). This action is part

of its ongoing efforts to reduce the levels of lead in food. In this

document, the agency is identifying the lead levels that it intends to

propose as new, lower lead specifications for the most heavily used

food and color additives and GRAS ingredients. Before proposing these

specifications, however, the agency is requesting information on

whether these levels are feasible, and, if they are not, information on

why higher levels will not endanger the public health, and on what

levels are feasible. The agency is requesting specific data and

information on the lead levels and the methods for detecting lead in

these substances. Additionally, the agency is requesting information on

the economic and environmental effects of lowering the lead levels.

DATES: Comments and information provided by May 5, 1994.

ADDRESSES: Submit written comments and information to the Dockets

Management Branch (HFA-305), Food and Drug Administration, rm. 1-23,

12420 Parklawn Dr., Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: Helen R. Thorsheim, Center for Food

Safety and Applied Nutrition (HFS-216), Food and Drug Administration,

200 C St. SW., Washington, DC 20204, 202-254-9511.

SUPPLEMENTARY INFORMATION: In this advance notice of proposed

rulemaking (ANPRM), the agency is announcing its intention to decrease

the amount of lead derived from food and color additives and GRAS food

ingredients in the diet through several actions. These actions are

prompted by the results of recent studies showing that deleterious

health effects are caused by much lower levels of lead than previous

results indicated, especially in fetuses, infants, and young children.

Also, the development of more sensitive analytical methods has made it

possible to detect lower lead levels in food ingredients.

This ANPRM has four purposes: (1) To discuss the toxic effects of

lead and to describe the multiple sources of lead in the human

environment; (2) to summarize actions that FDA and other Federal

agencies have taken to reduce lead exposures; (3) to discuss available

data and potential exposures to lead from the consumption of food,

including food and color additives and GRAS ingredients used in food;

and (4) to describe the need for new petitions for moderate and high

consumption food and color additives and GRAS ingredients to include

specific information on the levels of lead in these substances. This

information is necessary to assess the substance's contribution of lead

to the diet, and, therefore, whether it is safe for its intended use.

The agency intends to propose new, lower lead specifications for

moderate and high consumption food ingredients that either are the

subject of premarket review or are currently in use, to ensure that the

amount of lead contributed to the diet from the use of these food and

color additives and GRAS ingredients is as low as feasible. The agency

intends to propose adopting specifications of 0.5 part per million

(ppm) for moderate consumption food ingredients and 0.1 ppm for high

consumption food ingredients, unless information is submitted to show

that such levels are not feasible and that higher specifications will

not endanger the public health. Finally, the ANPRM requests specific

information on the lead levels and the methods used to detect lead in

the moderate and high consumption substances identified and on the

economic and environmental effects of lowering the lead levels in these

food and color additives and GRAS ingredients. FDA will review the

information provided in response to this ANPRM before it proposes

modifications to the current specifications for lead in these food and

color additives and GRAS ingredients.

I. Background

A. Lead Toxicity

Lead affects numerous essential body functions and has no known

physiological value. The primary targets of lead are the central and

peripheral nervous systems, the kidneys, and red blood cells. Recent

scientific evidence indicates that lead has deleterious effects on

human health at levels that were once thought to be innocuous. In fact,

there is no known level of lead intake that does not produce adverse

health effects.

FDA discussed the well-documented adverse health effects of lead in

an ANPRM on lead in food published in the Federal Register of August

31, 1979 (44 FR 51233); in a proposed rule on the migration of lead

from ceramic pitchers published in the Federal Register of June 1, 1989

(54 FR 23485); in a proposed rule on tin-coated foil capsules for wine

bottles published in the Federal Register of November 25, 1992 (57 FR

55485); and in a proposed rule on lead-soldered food cans published in

the Federal Register of June 21, 1993 (58 FR 33860). Also, the Centers

for Disease Control and Prevention (CDCP) discuss lead's effects in

their 1991 document entitled ``Preventing Lead Poisoning in Young

Children'' (Ref. 1).

In this ANPRM, FDA's primary concern is the effects of low levels

of lead on fetuses, infants, and children from consumption of food and

color additives and GRAS ingredients used in food. The adverse health

effects of lead exposure in fetuses, infants, and children occur at

lower blood lead levels than in adults. In particular, lead is harmful

to the developing major organs, such as the brain and nervous system,

of these sensitive population groups. Fetuses are sensitive to maternal

dietary lead intake, especially during the development of their nervous

systems. Further, infants and children ingest and absorb a larger

amount of lead per unit of body weight than adults, and they also

retain a larger fraction of absorbed lead.

Blood lead levels of a large number of children in the United

States remain above the toxicity standards recommended by the CDCP

(Ref. 1). Additionally, recent studies show a correlation between

impaired childhood development and lead exposure at levels as low as 10

micrograms/deciliter (g/dL) of lead in blood and below.

Decreased stature or growth, decreased hearing acuity, impaired

neurobehavioral development, and decreased intelligence have all been

linked to these low levels of lead exposure in children (Ref. 1). Lead

also interferes with the synthesis of vitamin D and heme, the iron

containing component of hemoglobin, at blood lead levels of 10 to 15

g/dL.

The symptoms of lead exposure at these low levels are not

pronounced and are therefore difficult to assess. A technique of

grouping data from different studies (meta-analysis), which enhances

the ability to detect a true effect, has been used to retrospectively

analyze 12 studies reported since 1981 on the relationship between

childhood lead exposures and neurobehavioral development (Ref. 2). The

results of this analysis strongly support the hypothesis that there is

an inverse relationship between lead exposure and childhood

intelligence quotient (IQ), even at very low doses. Similarly, a

coordinated study by eight countries showed a significant relationship

between increases in blood-lead concentration and decreases in

behavioral test performance for blood-lead levels ranging from 5 to 60

g/dL (Ref. 3).

Long-lasting adverse effects from low level childhood lead

exposures have also been observed. Early postnatal exposure results in

decreased cognitive performance in the preschool and early school years

(Refs. 4 and 5). Academic success and the fine motor skills of young

adults were also shown to be inversely related to the amount of lead in

the teeth shed by children in the first and second grades (Ref. 6).

Fetuses are also at risk to low levels of lead. The available data

show that the placenta is not a significant barrier to fetal lead

uptake. Maternal and umbilical cord blood-lead levels of 10 to 15

g/dL are associated with reduced gestational age and reduced

weight at birth (Ref. 4). Additionally, there are several studies in

which prenatal blood-lead levels were monitored, followed by monitoring

of the blood-lead level and childhood development for several years

after birth. In most of these studies, prenatal exposures were

associated with slower sensory motor development and delayed early

cognitive development (Ref. 1). Some of these associations may decrease

as the child ages, if postnatal exposures are low, and subsequent

socioeconomic conditions are favorable (Ref. 7).

Adult exposure to lead has been associated with higher occurrences

of cardiovascular disease when blood lead levels are as low as 25 to 30

g/dL (Ref. 8). In particular, there is an increased incidence

of high blood pressure, which may lead to an increase in hypertension-

related diseases. Red blood cell protoporphyrin elevation and

peripheral nerve dysfunction have also been observed at these same

blood lead levels (Ref. 8).

As the amount and duration of lead exposure increases, lead's

effects on the body become more severe. Blood-lead levels above 40

g/dL in all population groups can result in permanent kidney

damage, acute anemia, peripheral nerve dysfunction, and severe

gastrointestinal symptoms. Higher levels of lead affect the central

nervous system. Blood levels greater than 80 g/dL in children

and greater than 100 g/dL in adults can lead to acute

encephalopathy, characterized by massive accumulation of fluid in the

brain, gross mental retardation in children, convulsions, coma, and

even death (Ref. 8).

B. Sources of Lead

Lead is ubiquitous in industrial societies. Known sources of lead

include paint containing lead-based pigments, leaded gasoline, and lead

solder. Lead exposure occurs through pathways such as food, air, dust,

soil, and water. For children under 5 years of age, lead-based paint

remains the primary source of high level lead poisoning, with ingestion

of dust and soils contaminated with this paint being the primary

exposure pathway. In contrast, low level lead exposure in all

population groups is often caused by contributions through a variety of

pathways, with no single source or pathway predominating. Because the

effects of lead from all sources are additive, contributions from any

single source should be well below the amount known to cause

deleterious health effects.

In 1990, FDA estimated that, on average, 16 percent of a 2-year-old

child's lead intake was derived from food (Ref. 9). Most of the rest of

the lead was ingested from dust (75 percent). FDA has also estimated

that women of childbearing age ingest 43 percent of their lead from

food and 53 percent from dust and water. Children, through play and

normal hand-to-mouth activities, ingest larger amounts of lead from

dust and soil than adults.

Lead is introduced into food through a variety of pathways. It can

enter the food chain through water, dust, soil, or air. Naturally

occurring levels of lead in the environment are generally negligible

compared to those caused by humans (Ref. 10). Lead in water comes

primarily from the plumbing systems used for water distribution.

Airborne lead, from the exhaust of cars and machinery that use leaded

gasoline and from industrial activities that emit lead, can be

deposited directly on plants. Lead is also deposited on soil from these

sources. In addition, lead in soils is in part the result of the

historical use of lead-based pesticides. Lead deposited on soil remains

a long-term source of lead exposure because it does not biodegrade or

decay, and it is immobilized by the organic component of soil (Ref.

10).

Food processing also contributes lead to food. Lead can be

introduced through the machinery and water used in food processing,

from food and color additives and GRAS ingredients used in food, and

from food packaging. Cans with lead-soldered seams have been a

predominant source of lead contamination in food in the recent past. If

lead-based paint is present in a food manufacturing or processing

facility, paint dust containing significant quantities of lead may also

contaminate the food.

II. Previous Regulatory Action on Lead

A. FDA Actions

FDA has been involved in reducing the amount of lead in the diet

since the 1930's. Initial efforts were aimed at controlling the use of

lead-containing pesticides on fruits and vegetables. Subsequent

attention has been directed at lead contributions from a variety of

sources including ceramicware, lead-soldered food cans, and tin-lead

capsules for wine bottles.

In the Federal Register of August 31, 1979 (44 FR 51233), the FDA

published an ANPRM (the 1979 ANPRM) that described the sources of lead

in foods, the health concerns arising from the presence of lead in

foods, and the agency's plan to reduce the level of dietary lead intake

derived from the use of lead solder in food cans. The 1979 ANPRM

identified the maximum tolerable level of total lead intake from all

sources. The notice also announced the agency's tentative plan to

reduce contributions of lead from other sources in foods and requested

information on existing lead levels in foods.

The agency also published a proposed rule in the Federal Register

of June 1, 1989 (54 FR 23485) that proposed limitations on the amount

of lead that could leach from ceramic pitchers (excluding creamers)

that are intended for food contact. This document also proposed that

decorative ceramicware that leaches high lead levels must be

permanently labeled or modified in such a way as to preclude its use

for holding foods. The agency recently revised its Compliance Policy

Guide to include lower enforcement level guidelines for ceramic

foodware (July 6, 1992, 57 FR 29734).

Beginning in 1992, FDA has accelerated its actions to reduce the

level of lead in food. In the Federal Register of November 25, 1992 (57

FR 55485), the agency published a proposed rule to prohibit the use of

tin-coated lead foil capsules as coverings on wine bottles. This action

was based on evidence that under ordinary conditions of use, lead in

these capsules can become a component of wine. In that document, the

agency discussed the relationship between lead exposure and lead in

blood and tentatively defined a provisional tolerable total intake

level (PTTIL) for lead from all food and non-food sources. The agency

calculated the PTTIL based on the most up-to-date knowledge of lead's

lowest toxic effect levels. The agency tentatively set the PTTIL at 25

micrograms per day (g/day) for pregnant women, who are

surrogates for fetal exposure, and 75 g/day for other adults.

These values are provisional because they are based on the current

lowest observed effect level (LOEL) of lead in the blood (30

g/dL for adults and 10 g/dL for infants, children,

and pregnant women), which may need to be reduced further if additional

research shows that even lower blood-lead levels cause adverse health

effects.

In a proposed rule published in the Federal Register of January 5,

1993 (58 FR 389), the agency proposed to establish a maximum level of

0.005 milligram per liter (mg/L) as the quality standard for lead in

bottled water.

In a proposed rule published in the Federal Register of June 21,

1993 (58 FR 33860), the agency proposed to ban the use of lead solder

for domestic and imported food cans. In that document, the agency

tentatively defined the PTTIL for infants and children. The agency used

the LOEL of 10 g/dL to arrive at a PTTIL of 6 g/day

for infants and children (Ref. 8). This lower PTTIL is based on the

fact that children absorb lead more efficiently than do adults. In a

notice published in the Federal Register of April 1, 1993 (58 FR

17233), the agency also announced emergency action levels for lead in

foods packed in lead-soldered cans. These action levels are an interim

measure to protect infants and young children from adverse effects that

could result from daily consumption of foods packaged in lead-soldered

cans, pending completion of the rulemaking to prohibit the use of lead

solder in food cans.

In a final rule published in the Federal Register of January 12,

1994 (59 FR 1638), the agency amended its regulations to require that

decorative ceramicware, which may leach hazardous amounts of lead into

food, bear adequate indications to distinguish it from ceramic foodware

(i.e., ceramicware intended for holding, storing, or serving food).

This rule requires a statement and a stick-on label on the exterior

surface of the decorative ceramicware that the piece is not for food

use, and that it may poison food. Alternatively, the rule provides that

a hole may be bored through the possible food-contact surface of the

piece.

B. Other Federal Agency Actions

The elimination of lead poisoning is a coordinated effort by

several Federal agencies. In 1988, the Agency for Toxic Substances and

Disease Registry (ATSDR) published a report to Congress summarizing the

nature and extent of lead poisoning in children. The report found that

in 1984, 17 percent of metropolitan preschool children had blood lead

levels that exceeded 15 g/dL (Ref. 11). In February 1991, the

Department of Health and Human Services announced a ``Strategic Plan

for the Elimination of Childhood Lead Poisoning.'' This document called

for a concerted, society-wide elimination effort and described the need

for a more comprehensive evaluation of blood lead levels and

environmental lead contamination (Ref. 1).

CDCP also addressed the issues of lead toxicity and poison

prevention in children in their October 1991 document entitled

``Preventing Lead Poisoning in Young Children'' (Ref. 1). This document

included multitiered program, based on blood lead levels, that CDCP

devised to replace the previous single definition of lead poisoning.

The CDCP threshold for initiating action to reduce lead exposure was

lowered from 25 g/dL to 10 g/dL in children because

of the large amount of data showing lead's deleterious effects on

development at blood lead levels of 10 g/dL and above. The

CDCP are also helping laboratories to improve the reliability of blood

lead measurements and are developing improved instrumentation for

analysis of blood lead levels.

In 1978, the Consumer Product Safety Commission (CPSC) banned both

paint containing more than 0.06 percent lead by weight and the

deliberate addition of lead to paint for use on residential surfaces,

toys, and furniture. In addition, in the Federal Register of April 30,

1992 (57 FR 18418), the CPSC announced that it was investigating the

further reduction of this maximum allowable limit to 0.01 percent.

Lead-based paint is still available for industrial, marine, and

military use.

In a plan for the abatement of lead-based paint published in 1990,

the U.S. Department of Housing and Urban Development (HUD) found that

approximately 74 percent of occupied, privately-owned houses built

before 1980 still contained lead-based paint. The CDCP report (Ref. 1)

summarizes the results of this report and discusses methods for

decreasing lead exposure in houses painted with lead-based paint.

The Environmental Protection Agency (EPA) has been working for many

years on the removal of lead in gasoline, pesticides, and, more

recently, drinking water (June 7, 1991, 56 FR 26460). EPA has also

recently released a report to Congress outlining a strategy to reduce

human lead exposures from the environment, as summarized in the CDCP

report (Ref. 1). As part of this strategy, EPA published a final rule

on June 30, 1993 (58 FR 35314), that decreased the minimum quantity of

several lead compounds, as emissions from manufacturing facilities,

that must be reported to the agency.

III. Lead in Food and Color Additives and Gras Ingredients

A. Exposure to Lead from Food and Food Ingredients

Based upon the results of FDA's Total Diet Study (the agency's

annual market-basket survey of foods (Ref. 12)), from 1988 through

1990, FDA estimates that 2-year-old children consume about 4.5

g of lead each day from food alone, while women of

childbearing age consume about 9 g/day (Ref. 9). For a 2-year-

old child, lead intake from food is nearly equal to the PTTIL of 6

g/day for lead from all sources, even though food is estimated

to account for only 16 percent of the child's total daily intake of

lead (Ref. 9).

In its 1988 report to Congress, ATSDR estimated that, in 1987,

approximately 1 million young children in this country consumed

sufficient lead in food to cause blood lead levels of 10 g/dL

and greater (Ref. 11).

The relation between dietary lead and lead uptake in the body is

complex. Absorption of lead from the gastrointestinal (GI) tract in

adults is normally about 10 to 15 percent, but it can be as high as 45

percent under fasting conditions (Ref. 8). This difference may be

important, for example, when foods containing lead are consumed between

meals. It has been empirically estimated that for low exposures,

resulting in blood lead levels of up to 30 g/dL, the ingestion

of 1 g of lead per day in the diet results in an increase of

0.04 g/dL of lead in the blood of adults (Ref. 13).

Children are even more efficient at absorbing lead through the GI

tract than are adults, with a rate of absorption of approximately 50

percent (Ref. 8). In children, for exposures resulting in blood lead

levels up to 10 g/dL, every microgram of lead ingested per day

from the diet increases the blood lead level by 0.16 g/dL.

This level is approximately four times as much lead in the blood per

equivalent dose as in adults.

B. Need for Action to Lower Lead Specifications

Since FDA began to regulate food additives in 1958, the agency has

generally considered that the public health was adequately protected by

specifications of 3 ppm for arsenic, 10 ppm for lead, and 40 ppm for

total heavy metals (as lead) (Ref. 14). The agency believed that these

specifications could readily be met in food additives produced under

current good manufacturing practice (CGMP) conditions, and that these

specifications would ensure that food additives would not contribute

significant amounts of heavy metals to the diet. The agency also

believed that the actual heavy-metal levels achieved through adherence

to CGMP's would be significantly lower than these limits (Ref. 15).

When the Food Chemicals Codex was established by the National

Academy of Sciences (NAS) in 1961, the Food Chemicals Codex committee

adopted these specifications for nearly all food additives. These

levels have remained until recently as the levels used as guidance in

establishing specifications in Food Chemicals Codex monographs for food

ingredients.

However, with today's increased knowledge of lead's deleterious

effects at low ingestion levels, it is necessary to decrease lead

specifications for food and color additives and GRAS ingredients to

protect the public health. Specifications must be set at the lowest

lead levels attainable through the diligent application of CGMP's to

ensure that lead is reduced to its lowest possible levels in food.

The potential exists, with the high current levels of lead

specifications, that food and color additives and GRAS ingredients will

contribute significant amounts of lead to the diet. Even if most food

ingredients do not contain the maximum amount of lead permitted by the

specifications, lead ingested from the use of food and color additives

and GRAS ingredients will comprise a small, although not readily

quantifiable, percentage of a person's total dietary lead intake.

Because low level lead exposure is often the result of contributions

from multiple small sources, significant reductions in a person's

overall lead exposure can result from reductions in the levels of lead

in many of those sources. Although some sources may be difficult to

control, the agency believes that industry has the ability to reduce

lead levels in food and color additives and GRAS ingredients, either

through tighter control of starting material purities or improvements

in manufacturing processes.

To illustrate the potential lead exposure from food and color

additives and GRAS ingredients, FDA has calculated the possible per

capita lead intake from the use of those additives and GRAS ingredients

that are added to the U.S. food supply in amounts greater than 25

million pounds per year\1\. These high consumption substances

(currently 38) constitute over 80 percent by weight of all substances

in the 1987 NAS survey. The agency recognizes that the absolute

poundages of these substances may not be accurately portrayed in the

survey because the information is voluntarily reported. However, the

agency believes that the data accurately reflect the relative ranking

of the substances. Therefore, the data are useful for illustrative

purposes and can serve as a means of prioritizing actions on food

ingredients based on relative usage levels.

The 38 substances are listed in Table 1 in decreasing order of

reported use, along with their maximum lead specifications. When

possible, the lead specifications that are either listed or referenced

in FDA regulations for lead or heavy metals (as lead) are shown. If no

lead specification is referenced in FDA regulations, the most recent

specification in the Food Chemicals Codex (Refs. 16 through 18) is

listed. For the few food substances that have no lead specification,

FDA used a lead level of 1 ppm to calculate the potential lead

exposure.

Table 1--Most Widely Used Food Substances and Their Current Lead Specifications\1\

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Substance\2\ Lead Limit\3\ ppm Substance\2\ Lead Limit\3\ ppm

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High fructose corn syrup 0.5 d-Sorbitol 10.0

Sucrose 0.5 Lactose -

Corn syrup 0.5 Calcium oxide 10.0

Corn gluten - Sodium bicarbonate 5.0

Soybean oil 0.1 Mono-diglycerides 10.0

Sodium chloride 4.0 Palm kernel oil 0.1

Sucrose liquid - Phosphoric acid 10.0

Corn oil 0.1 Maltodextrin 0.5

Dextrose 0.1 Iron, reduced 25.0

Whey 10.0 Niacin 20.0

Calcium carbonate 10.0 Sodium phosphate, di- 10.0

Coconut oil 0.1 Monosodium glutamate 10.0

Caramel 10.0 Peanut oil 0.1

Diatomaceous earth 10.0 Casein 5.0

Starch, food, modified 5.0 Azodicarbonamide 10.0

Cottonseed oil 0.1 Calcium sulfate 10.0

Cocoa butter substitute 10.0 Sulfuric acid 5.0

Sodium hydroxide 10.0 Glycerin 5.0

Citric acid 10.0 Sodium citrate 10.0

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\1\Substances are listed in decreasing order of poundage. High volume substances (poundages greater than 100

million pounds per year) are listed on the left, while moderate volume substances (25 million to 100 million

pounds per year) are on the right.

\2\Boldface substances have specifications in the Code of Federal Regulations.

\3\The type of lead specification is indicated by the font type: Boldface type means that the level is an actual

lead specification, italics mean that the lead level is from a specification denoted ``heavy metals as lead,''

and a dash indicates that there is no available lead specification.

Based upon the lead levels listed and the per capita intake of

these substances, FDA calculates that the theoretical maximum per

capita intake of lead from the food use of these 38 widely used

substances could reach 164 g/day if all lead levels were at

their maximum specification limits. Although it is clear from FDA's

total diet study (Ref. 9) that the amount of lead consumed (4.5

g/day for a 2-year-old child and 9 g/day for women of

childbearing age) is not nearly as high as the sum of these

specifications would permit, the calculation illustrates the potential

lead exposure if food and color additives and GRAS ingredients were

consistently produced with lead levels near the specification limits.

It also demonstrates that these specification levels are collectively

well in excess of the levels of lead in the ingredients actually being

added to food.

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\1\This calculation is based upon disappearance data from a 1987

survey by the NAS on the quantities of food substances added by the

U.S. industry to food (Ref. 19). FDA recognizes that disappearance

data identify the amounts of substances available for use in food

and food processing, but do not necessarily mean that all of these

amounts are consumed in food.

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The agency has also calculated the potential effect on the

ingestion of lead if all of the lead specifications for these 38

substances were reduced. If the agency were to replace the current lead

specifications with lower lead levels of 0.1 ppm for high volume

substances (those with disappearance poundages greater than 100 million

pounds/year) and 0.5 ppm for those of moderate volume (between 25

million and 100 million pounds per year), FDA has estimated that the

theoretical per capita intake of lead from these 38 most widely used

food ingredients could be reduced from 164 g/day to 13

g/day (Refs. 19 and 20). Although lead levels are generally

not as high as current lead specifications allow, lowering these

specifications is likely to have the effect of lowering lead exposure.

Manufacturers will be more concerned about monitoring and controlling

the lead content of their products to ensure that the lead levels are

substantially below the new specification levels, and that the normal

variations in lead content that occur from batch to batch do not

produce a violative product. Also, lower lead specifications will

protect subsets of the population that might eat food that has been

produced with food ingredients containing unusually high lead levels,

if, for example, a particular manufacturer uses a process that results

in the food ingredient having a higher level of lead than average.

As a further illustration, the agency has calculated the potential

decrease in lead intake from reduction of lead specifications in a

specific color additive, caramel. Caramel currently has a 10 ppm lead

limit specification in FDA regulations (21 CFR 73.85). However, the

food industry usually controls for contaminants at levels that are

significantly lower than the established specification levels to ensure

that all production batches will be in compliance. From informal

conversations with industry, the agency believes that a reasonable

control level might be one-fifth the specification level. Using the

data from the 1987 NAS poundage survey (Ref. 19), and assuming that all

caramel is produced with lead levels at one-fifth the specification, or

2 ppm, the agency calculates that the potential per capita lead

exposure from caramel could still be as high as 1.6 g/day.

Reducing the specification to 0.1 ppm could result in a potential 100-

fold reduction in lead levels in caramel.

High fructose corn syrup (HFCS), one of the most heavily used food

ingredients in the United States according to the NAS poundage survey,

illustrates the efforts industry has made to aid FDA and a Food

Chemicals Codex committee in setting lower lead specifications that

more accurately reflect actual lead levels. HFCS has been commercially

produced since 1967, and FDA listed HFCS containing 43 percent fructose

as GRAS in 1983 (21 CFR 182.1866). The listing, however, does not

include any specifications for impurities such as lead. In the absence

of lead specifications, industry was guided by the Food Chemicals Codex

committee's general impurities policy that included a 10 ppm lead

specification (Ref. 16). It was not until 1986 that a Food Chemicals

Codex monograph was developed for HFCS, which set a lead specification

of 1 ppm (Food Chemicals Codex, 3d ed., 2d supp. (Ref. 17)). The Food

Chemicals Codex lead specification was further reduced in 1992 to 0.5

ppm as a result of cooperative interactions between FDA, the Food

Chemicals Codex, and industry. In response to a request by the agency

in 1990, industry provided preliminary data on lead levels in a small

sampling of HFCS measured by methods that are more sensitive than

routine quality control methods. Actual lead levels ranged between

0.002 and 0.073 ppm in the samples analyzed (Refs. 21 and 22). Although

measurements with this level of sensitivity are not yet done on a

routine basis, these results suggest the actual amounts of lead in

HFCS. Using these measurements, a 12-ounce (oz) can of soda that

contains 10 percent HFCS probably contains lead in the range of 0.07 to

2.6 g, whereas existing lead specifications would allow 18

g of lead. Lowering the specification for lead in HFCS to 0.1

ppm would reduce the maximum allowable lead from HFCS in a 12 oz can of

soda to 3.6 g.

C. Changes in Food Chemicals Codex Lead Specifications

As part of FDA's initiative to reduce lead in food, the agency has

been working with the Food Chemicals Codex committee of the NAS to

review lead specifications for selected food ingredients. The 3d

edition of the Food Chemicals Codex and its four supplements contain

specifications and analytical methodologies for over 900 food

ingredients. The specifications are used by food processors and

manufacturers of food ingredients in the United States and in other

countries as guidelines for their products' purity. The specifications

are also often incorporated by reference into FDA's regulations for

food and color additives and GRAS ingredients.

The agency's concerns regarding lead levels in food ingredients

were presented to the Food Chemicals Codex committee during a workshop

on May 2, 1991. For many substances, the Food Chemicals Codex currently

specifies a 10-ppm lead limitation (see section III.B. of this

document). Following the workshop, the Food Chemicals Codex committee

updated its policy for establishing lead specifications for food

ingredients. Previously, lead specifications were set at the lowest

practicable levels based on CGMP and the capability of analytical

methodology to determine the lead level in individual food ingredients.

The Food Chemicals Codex committee's policy, announced in the Federal

Register of July 15, 1993 (58 FR 38129), now provides that the Food

Chemicals Codex will set lead specifications by also considering the

estimated lead intake from use of the food ingredient and the potential

health hazard of these intake levels, in a fashion similar to that

which the agency is considering.

As an outgrowth of the Food Chemicals Codex committee workshop, new

and revised lower lead specifications have been published for several

food ingredients in the Food Chemicals Codex (3d ed., 3d supp. (Ref.

18)). For example, included are lead specifications of 0.1 ppm for

dextrose and fructose and 0.5 ppm for less refined products, such as

glucose syrups, maltodextrin, and polydextrose. The Food Chemicals

Codex committee has been reviewing and revising the lead specifications

for other food and color additives and GRAS ingredients as well (Ref.

23). The Food Chemicals Codex committee is expected to continue

reducing lead specifications in future monograph revisions for

inclusion in the fourth edition of the Food Chemicals Codex.

IV. Changes in FDA Lead Specifications

Because of the possibility that significant amounts of lead might

be introduced into food from regulated food and color additives and

GRAS ingredients, and because of the increased knowledge of the

deleterious health effects of low level lead exposure, FDA has started

to take action to limit the potential dietary intake of lead from these

sources. Based on the considerations discussed in section III. of this

document, the agency is focusing on high and moderate consumption

substances, such as those listed in Table 1 of this document.

The agency has begun requesting that information on lead levels be

included in certain food and color additive and GRAS affirmation

petitions. FDA is asking that petitions for either new uses of

regulated high and moderate consumption substances, or new substances

that are expected to be consumed in significant quantities, show that

lead levels in the petitioned products are as low as CGMP's allow.

Given the toxicity of lead, such evidence is necessary if the agency is

to make a determination on the safety of the additive for its proposed

use. The agency will evaluate the data that it receives on lead levels

during the petition review process and set lead specifications at

levels that are necessary to ensure that there is a reasonable

certainty of no harm from use of the additive.

Lower specifications, to be meaningful, will need to be supported

by analytical methods that allow quantification of lead at the reduced

levels. Recent advances in instrumentation should allow for reliable,

quantitative detection of lead in food ingredients at much lower levels

than possible with previous analytical methods. For example, in the

Food Chemicals Codex (3d ed., 3d supp. (Ref. 18)), a graphite furnace

atomic absorption spectrophotometric method is described that detects

lead in substances such as edible oils at levels less than 1

g/g (1 ppm) of lead. A similar method has been developed for

nutritive sweeteners (Ref. 24). Development of more sensitive routine

analytical procedures or expertise in more sophisticated methods will

facilitate routine testing for lead below 0.1 ppm and will enable

industry to further control and eliminate lead from food ingredients.

Thus, the agency is asking petitioners to provide analytical

methodologies that are capable of detecting lead at sub-ppm levels and

to show that these methodologies have been validated.

FDA recognizes the need to lower its lead specifications for high

and moderately high consumption food and color additives and GRAS

ingredients to ensure that their use is safe. Thus, in the absence of

persuasive comments to the contrary, the agency intends to propose

setting specifications at 0.1 ppm lead for high-poundage ingredients

(greater than 100 million pounds per year, such as substances in the

left column of Table 1) and 0.5 ppm lead for moderately high-poundage

ingredients (between 25 and 100 million pounds per year, such as

substances in the right column of Table 1). FDA plans to propose

establishing these specifications for new ingredients, new uses of

previously regulated ingredients, and currently regulated ingredients.

Also, FDA is considering only adopting Food Chemicals Codex lead

specifications for individual ingredients when it finds that the levels

are low enough to protect the public health.

Comments on these approaches to setting specifications for lead,

and suggestions for alternative approaches for developing consistent

lead specifications for all current and future uses of food and color

additives and GRAS ingredients that still protect the public health,

are requested.

V. Request for Information

Although FDA has extensive information concerning lead in its

files, additional information on the following topics will greatly

assist the agency both in setting specifications for lead in food and

color additives and GRAS ingredients and in minimizing the exposure to

lead in a consistent manner:

1. Current data on actual lead levels in: (a) Food and color

additives and GRAS ingredients, the variation in these levels, and

suggested lead specifications for each substance. Of particular

interest are the high consumption substances in the left column of

Table 1 of this document and the moderate consumption substances in the

right column of Table 1. Also of interest are other substances that,

although consumed at a lower rate, contain sufficiently high levels of

lead to be of concern; (b) agricultural commodities that are raw

materials for many food ingredients; and (c) nutrient supplements

(e.g., calcium, iron).

2. Analytical methods for detecting sub-ppm levels of lead in food

components, including detection limits, reliability of the methods for

different food and color additives and GRAS ingredients, and validation

data. Of particular interest are improvements in graphite furnace

atomic absorption spectrophotometry and studies of its applicability to

the 38 substances listed in Table 1.

3. Information on the potential economic impact, if any, associated

with the manufacture of the 38 food and color additives and GRAS

ingredients listed in Table 1 if the lower lead levels are adopted. FDA

is required to assess the economic consequences of any regulation it

proposes, but it does not possess data that would permit detailed

assessment of the economic impact of adopting lower lead

specifications.

4. Information on the potential environmental impact that may be

associated with the manufacture of the 38 food and color additives and

GRAS ingredients if lower lead specifications are adopted. Under the

National Environmental Policy Act, FDA must consider the environmental

impact of its actions. However, the agency does not now possess the

data that would permit detailed analysis of the environmental impact of

adopting lower lead levels. Therefore, the agency is requesting

environmental information that includes, but is not limited to, the

following: (a) A description of the additional steps, if any, required

to produce these food and color additives and GRAS ingredients with the

reduced lead specifications and of the environmental impact of these

steps; (b) the environmental impact of additional testing, if any,

performed to ensure compliance with the lower lead specifications; and

(c) a description of measures that could be taken to avoid or mitigate

adverse environmental impacts, if such impacts are predicted to result

from this action.

VI. Conclusion

FDA has had a longstanding goal of reducing lead exposure from all

dietary sources. Because lead is ubiquitous, and exposure to lead is

from a multitude of different sources, lead levels from each source

must be sufficiently low to ensure that a person's total lead exposure

is not harmful. The agency believes that lead specifications in food

and color additives and GRAS ingredients can be lowered to help achieve

this goal and protect the public health. Therefore, the agency intends

to lower lead specifications in food and color additives and GRAS

ingredients that are consumed in large amounts by the general

population to levels that will offer adequate protection.

FDA plans to propose lead specifications of 0.5 ppm for moderate

consumption food ingredients and 0.1 ppm for high consumption food

ingredients. The agency is requesting information on current lead

levels in food ingredients and analytical methods for determining these

lead levels, and on the economic and environmental effects of complying

with these specifications. The information received in response to this

ANPRM will be used to determine the feasibility of adopting these

target specifications. The agency intends to propose these

specifications unless information is submitted to show that such levels

are not feasible and higher specifications will not endanger the public

health.

VII. 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. CDCP, Department of Health and Human Service, Public Health

Service, ``Preventing Lead Poisoning in Young Children,'' October

1991.

2. Needleman, H. L., and C. A. Gatsonis, ``Low-Level Lead

Exposure and the IQ of Children,'' Journal of the American Medical

Association, 263:673-678, 1990.

3. Winneke, G., A. Brockhaus, U. Ewers, U. Kramer, and M. Neuf,

``Results from the European Multicenter Study on Lead Neurotoxicity

in Children: Implications for Risk Assessment,'' Neurotoxicity and

Teratology, 12:553-559, 1990.

4. Bellinger, D., A. Leviton, C. Waternaux, H. Needleman, and M.

Rabinowitz, ``Longitudinal Analyses of Prenatal and Postnatal Lead

Exposure and Early Cognitive Development,'' New England Journal of

Medicine, 316:1037-1043, 1987.

5. Baghurst, P. A., A. J. McMichael, N. R. Wigg, G. V. Vimpani,

E. F. Robertson, R. J. Roberts, and S. L. Tong, ``Environmental

Exposure to Lead and Children's Intelligence at the Age of Seven

Years: The Port Pirie Cohort Study,'' New England Journal of

Medicine, 327:1279-1284, 1992.

6. Needleman, H. L., A. Schell, D. Bellinger, A. Leviton, and E.

N. Allred, ``The Long-Term Effects of Exposure to Low Doses of Lead

in Childhood: an 11-year Follow-up Report,'' New England Journal of

Medicine, 322:83-88, 1990.

7. Bellinger, D., J. Sloman, A. Leviton, M. Rabinowitz, H. L.

Needleman, and C. Waternaux, ``Low-Level Lead Exposure and

Children's Cognitive Function in the Preschool Years,'' Pediatrics,

87:219-227, 1991.

8. Memorandum, dated November 18, 1991, from Contaminants Team,

Standards and Monitoring Branch, to Additives Evaluation Branch,

``Clarification of Terminology Used in the Development of the

Provisional Total Tolerable Intake Levels for Lead.''

9. Bolger, P. M., C. D. Carrington, S. G. Capar, and M. A.

Adams, ``Reductions in Dietary Lead Exposure in the United States,''

Chemical Speciation and Bioavailability, 3:31-36, 1991.

10. Elias, R. W., ``Lead Exposures in the Human Environment,''

in Dietary and Environmental Lead: Human Health Effects, edited by

K. R. Mahaffey, Elsevier Science Publishers, B. V., Amsterdam, pp.

79-107, 1985.

11. Agency for Toxic Substances and Disease Registry, Public

Health Service, ``The Nature and Extent of Lead Poisoning in

Children in the United States: A Report to Congress,'' pp. (VI-44)-

(VI-49), July 1988.

12. Pennington, J. A. T. and E. L. Gunderson, ``History of the

Food and Drug Administration's Total Diet Study--1961 to 1987,''

Journal of the Association of Official Analytical Chemists, 70:772-

782, 1987.

13. Carrington, C. D. and P. M. Bolger, ``An Assessment of the

Hazards of Lead in Food,'' Regulatory Toxicology and Pharmacology,

16:265-272, 1992.

14. Excerpts from ``Chemical Problems Encountered in the

Administration of the Food Additives Amendment,'' a speech given by

L. L. Ramsey at ``Symposium on Analytical Methods for Food Additive

and Pesticide Chemicals,'' American Chemical Society, New York, NY,

September, 1960.

15. Excerpt from Food Chemicals Codex Advisory Panel Bulletins,

December 1962, letter from Dr. Henry Fischbach, FDA, to Dr. Justin

L. Powers, Food Chemicals Codex Director, NAS.

16. Food Chemicals Codex, 3d ed., National Academy Press,

Washington, DC, 1981.

17. Food Chemicals Codex, 3d ed., 2d supp., National Academy

Press, Washington, DC, 1986.

18. Food Chemicals Codex, 3d ed., 3d supp., National Academy

Press, Washington, DC, 1992.

19. Memorandum, dated July 17, 1992, from Food and Color

Additives Review Section, to Indirect Additives Branch, ``Lead in

Food Additives--Hypothetical Effects on Dietary Lead Intake of

Lowering Lead Specifications.''

20. Memorandum, dated December 16, 1993, from Chemistry Review

Branch, to Indirect Additives Branch, ``Lead in Food Additives.

Fructose Disappearance Data and Predicted Lead Intake. Request for

Additional Information dated 12-14-93.''

21. Letter, dated February 5, 1990, from Kyd D. Brenner, Corn

Refiners Association, Inc., to John W. Gordon, FDA.

22. Letter, dated March 22, 1990, from Kyd D. Brenner, Corn

Refiners Association, Inc., to John W. Gordon, FDA.

23. Bigelow, S. W., ``Role of the Food Chemicals Codex in

Lowering Dietary Lead Consumption: A Review'' Journal of Food

Protection, 55:455-458, 1992.

24. ILSI North America, Subcommittee on Trace Minerals in Foods,

``Report to the FCC Committee on Methodology for Lead in

Sweeteners,'' June 28, 1993.

VIII. Comments

Interested persons may, on or before May 5, 1994, submit to the

Dockets Management Branch (address above) written comments regarding

this advance notice of proposed rulemaking. Two copies of any comments

are to be submitted, except that individuals may submit one copy.

Comments are to be identified with the docket number found in brackets

in the heading of this document. Received comments may be seen in the

office above between 9 a.m. and 4 p.m., Monday through Friday.

Trade secret and commercial confidential information should be

submitted to the contact person identified above. Trade secret and

commercial confidential information will be protected from public

disclosure in accordance with 21 CFR part 20.

Dated: January 12, 1994.

Michael R. Taylor,

Deputy Commissioner for Policy.

[FR Doc. 94-2472 Filed 2-3-94; 8:45 am]

BILLING CODE 4160-01-F