Center for Food Safety & Applied Nutrition Office of Premarket Approval September 1995 (Effective June 18, 2001, Office of Premarket Approval is now Office of Food Additive Safety. See updated contact information) |
The US Food and Drug Administration (FDA)
regulates substances either intentionally added
to food to accomplish a proven technical effect
or inadvertently added through contamination, processing, or
packaging.(1) The premarket
approval process for food additives requires an
estimate of the probable consumer exposure to
the additive to determine whether its use or
presence in a food at a given concentration is safe.
The intent of this document is to provide an understanding of
the databases and methodologies used by the Office of Premarket
Approval (OPA) in FDA's Center for Food Safety and Applied
Nutrition to estimate exposure to food additives and other
substances (e.g., chemical contaminants) found in the diet. This
document is primarily directed at petitioners for food additive
regulations. Illustrative examples of the calculations that the
technical reviewers of OPA's Chemistry Review Branch
(CRB)(2) perform
to obtain the legally-required estimate of probable exposure
for substances added to food are included. It should also be
useful to other parties interested in the means by which exposures
to food additives and chemical contaminants can be estimated.
The key determinant in the safety evaluation of
a substance found in or added to the diet is the
relation of its probable human exposure to the
level at which adverse effects are observed in toxicological
studies.(3)
Simply, "the dose makes the poison." The implications of this
adage as it pertains to food can be illustrated with two
clear examples. While "pure" water can be viewed
as the safest of foods, excessive intake can lead
to a potentially fatal electrolyte imbalance.
Conversely, pure concentrated sulfuric acid
destroys human tissue, but it is affirmed as
"Generally Recognized as Safe" (GRAS) by the FDA
in the Code of Federal Regulations
(CFR)(4)
when used to control pH during the processing of
alcoholic beverages or cheeses. Clearly, the use
and the dose (i.e., exposure) are overriding
considerations when discussing the safety of a component of food.
The definition of a food additive in section 201
(s) of the Federal Food, Drug, and Cosmetic Act,
as amended (hereinafter referred to as "the Act")
refers to substances whose intended use results
directly or indirectly in the substance becoming
a component of food. The FDA refers to direct
food additives as those added to a food to
accomplish an intended effect. Indirect additives are those
that unintentionally, though predictably, become components of food.
Components of plastic packaging materials that
can migrate to food are indirect additives.
The differences between direct and indirect
additives are such that different methodologies
are necessary to prepare estimates of probable
human exposure. It is relatively straightforward
to determine how much of a direct additive could
be present in any given food. Indirect additives,
on the other hand, cannot be treated in a
parallel manner due to the great variety of
packaging materials (glass, paper, coated papers,
plastics, laminates, and adjuvants used in their
manufacture), and the great variability in the
use of packaged foods. Also, the fact that these
additives are not intentionally added to food
(which is to say that "use levels" in food cannot
be defined), makes direct comparisons with
methods used for estimating exposures to direct additives
inappropriate.(5)
This document deals only with estimating
exposure to direct additives and chemical
contaminants. The procedures used to estimate
exposure to chemical contaminants in food
(including naturally occurring toxicants, such as
mycotoxins) are essentially the same as those
used for direct additives. Thus, contaminants
will be considered in the discussion of direct
additive exposure estimation. The procedures
discussed herein are equally applicable to color additives,
GRAS substances, prior-sanctioned ingredients, and pesticide
residues.(6)
Direct food additives are regulated in 21 CFR 172
(GRAS ingredients are regulated in 21 CFR 182 and
184). Secondary direct additives, a sub-class of
direct additives, are primarily processing aids.
These materials, which are used to accomplish a
technical effect during the processing of food
but are not intended to serve a technical
function in the finished food, are regulated in 21
CFR 173. Secondary direct food additives are
like indirect additives in that only residues of
the additive, or its components, are typically
found in the food. The estimate of daily intake
(EDI) for a secondary direct additive, however, is
generally calculated in the same manner as those
for direct additives and will be considered in this document.
Chemical contaminants are substances that are
present in food or food additives either
unavoidably or unintentionally. Typically, there
are two types of chemical contaminants that are
encountered: (1) those present in food additives
(generally, from manufacture), and; (2) those
present in food itself (due to manufacture,
natural, or environmental contamination, e.g.,
lead, aflatoxin, or polychlorinated biphenyls).
The practical difference between estimating
exposure for contaminants and additives is the
derivation of the concentration of the
substance. Contaminant concentrations are
usually determined experimentally, while additive
concentrations or use levels are proposed by a
petitioner(7)
for specified uses of a food additive. The different procedures
used for estimating exposure to additives and
contaminants will be discussed in the remainder
of this document, with detailed examples in the last section.
There are a number of sources available to OPA
for data used in estimating exposure to substances in the
diet,(8) including:
Each of these sources has advantages and
limitations. For a number of reasons, including
cost and availability, breadth of data, and ease
of data manipulation, OPA relies primarily on
data taken from food consumption surveys. OPA
has not used data from body burden/excretion
measurements or weights and analyses of foods
for estimating exposure. In the following
sections, OPA's use of the data from consumption
surveys, disappearance data, and market basket
surveys will be outlined.
OPA's use of food consumption survey data for
estimating exposure to substances in the diet
involves the linking of food intakes with
independently-determined concentrations of the
substances in foods. Because distributions of
food intakes are generally available from a food
consumption survey, estimates for mean exposure
or for any point on the population distribution
(e.g., 50th or 90th percentile) are possible.
OPA regularly uses national food consumption
surveys to estimate dietary exposure to
substances. These surveys measure food intake
by one or more methods: 24-hour intake recall,
food intake record (also called food diary), and
food frequency record or recall. For the first
two methods, participants recall or record the
amounts and types of each food eaten during the day. For the food
frequency methods, participants record or recall only the number of
occasions each food was consumed over a time
period that may vary from a few days to more
than a year.(9)
These eating-occasion frequencies are multiplied by an appropriate
portion size (based on age-sex considerations) to obtain
estimates of the daily food intake. Useful
surveys include consumption data for foods
eaten both at home and away from home.
The USDA has surveyed food use by US households
since 1936. In the 1960s, the surveys were
expanded to include food intake by individuals.
Traditionally, these surveys appraised the
nutritional adequacy of American diets rather
than the safety of food with respect to
additives or contaminants. However, the
information on food intakes found in the USDA
surveys is now frequently used to assess
exposure to additives and contaminants.
Marketing research groups in the United States,
such as the Market Research Corporation of
America (MRCA) and the National Purchase Diary
(NPD) have also surveyed the food consumption
patterns of individuals and households for the
food industry. Surveys of this type are not
common throughout the rest of the world, but the
World Health Organization (WHO) has emphasized
the need for such data in a publication
prescribing its guidelines for monitoring intakes of chemical
contaminants.(10)
A review of food consumption surveys throughout the world was
published by the Food and Agriculture Organization (FAO) in
1985.(11)
The FASEB report issued by its Life Sciences
Research Office in 1988 examined in detail the
theory behind the calculation of exposure
estimates.(12)
This report, prepared for the US
FDA, listed several food consumption databases
for use in estimating food intakes. These
included national food consumption surveys
conducted by the US government, such as the
USDA's Nationwide Food Consumption Survey (NFCS)
and Continuing Survey of Food Intake by
Individuals (CSFII), as well as the National Health
and Nutrition Examination Survey (NHANES), and
commercially sponsored surveys, such as the
MRCA Menu Census and the NPD Eating Trends
surveys. OPA has historically relied on the
USDA's 3-day Nationwide Food Consumption
Surveys and the Market Research Corporation of
America's Surveys (herein referred to as the
MRCA Survey(13)).
The USDA 3-day surveys, the
CSFII, and the MRCA 14-day surveys are further
described below.
3-Day USDA/NFCS Survey and the CSFII
Summary reports from the US Department of
Agriculture's 3-day Nationwide Food Consumption
Survey of 1977-78 were published in 1982 as
"Foods Commonly Eaten by Individuals". The
survey was repeated during 1987 and 1988, but,
due to statistical problems resulting from low
response rates in certain sub-populations, the
results have not yet been published in summary
report form.(14)
The information was collected in
two steps: the first involved an interviewer-recorded recall of
all of the foods consumed during the first day; the second part was 2-day
a recall/report completed by the participant.
Detailed instructions, including measuring cups, spoons, and a ruler,
were given to the participants to aid in accurately reporting their
intakes. The participants were selected to avoid
geographical bias, and the survey was conducted over a
twelve month period to avoid any seasonal bias in eating habits.
The data in the summary reports are presented in
tables, each addressing the intake of a broad
food class, such as meat and poultry, or an
associated sub-class, such as fried chicken. All
of the reported intake figures are on an
eaters-only(15)
basis. The percentage of eaters in each
classification is included. The raw data from
USDA surveys have been accessible to reviewers
at CRB; however, such access, until recently, has
not been routine. For many years, the summary
report food intake data from the 1977-78 survey
have been used in estimating exposure.
The information available from this survey
includes: 1) the total number of individuals
consuming the food on one, two, or all three of
the survey days; 2) quantities of each food type
consumed, averaged over the three days or
averaged for individuals consuming the food on
one, two, or three days; and 3) the quantity
consumed per eating occasion. The data
pertaining to quantities consumed are presented
both as overall averages and as a percentile
distribution, ranging from 5th to 99th percentile
intakes. Maximum quantities consumed on one day, three days,
and per eating occasion are also included in the same formats.
The 1987-88 NFCS was conducted using the same
data collection and reporting techniques used in
the 1977-78 survey. The raw data from the 1987-88
NFCS, and the related 1989-90, 1990-91, and
1991-92 CSFII's, are accessible to CRB through a
proprietary software package designed to use
the data in producing exposure
estimates.(16)
The CSFII planned for 1994-1996 will be a two day survey, as will
future NFCS surveys. Non-sequential days will be surveyed in order
to assure that additional intra-individual bias is
not introduced into the survey by the first
day's food choices influencing choices made on the second survey day.
The MRCA 14-Day Survey
The Market Research Corporation of America's 14-day
food-frequency survey had until recently
been a primary source of food intake information
for OPA. The survey, which is updated annually,
is intended to examine the number of eating
occasions per day for any food consumed over a
14-consecutive day period. The most recent data
available to OPA were compiled during the five
year period from 1982 to 1987. This survey, which
included over 25,000 participants, was also conducted
in a manner to avoid geographical and seasonal eating biases.
The MRCA survey data are recorded by a single
member of each surveyed household, usually the
female head. For each member of the household,
the number of eating occasions for each specific
food consumed, both in-home and away-from-home,
is recorded. Following the survey period, the
recorder would submit the age, sex, weight, and
diet status for each member of the household.
The frequencies of eating occasions thus obtained need to be
linked to appropriate portion size data to obtain the food intakes
necessary for estimating exposure to substances in food
(see discussion below in
"Modeling exposure
analysis".) This form
of data collection allows estimates to be prepared for specific
age/sex/demographic groupings, as well as for
specific conditions, such as diabetics.
In the United States, information on the weight
of commodities entering commerce is available
annually from the Economic Research Service of
the USDA.(17)
Quantities are measured by deducting data on exports, year-end
inventory, and non-food use from data on production,
imports, and beginning inventories. These data are sometimes referred
to as "disappearance" data because they represent the disappearance
of food into the marketing system. Annual disappearance figures
for a food commodity can be divided by the national population and
by 365 days to obtain a "per capita" estimate of the
food that is available for consumption per day
(see example: Estimated Daily Intake
for an Amino Acid in Sweet Pickles).
The food industry also measures the disappearance of specific
products into the market. These data are usually gathered to
observe marketing trends and lack the
specificity needed for use by regulatory bodies.
When the data obtained reflect disappearance of
all of the product being monitored, such as total
alcohol or carbonated beverage consumption,
crude estimates of per-capita intake can be made.
Food disappearance data may overestimate actual per
capita consumption because they include spoilage and waste
accumulated in the marketing system and in the home, and some food
that is not available for human consumption, such
as turkey parts used in pet
foods.(18)
For example, in 1987-88, the estimate of food energy
available for consumption per capita per day in
the United States was about twice the estimate
of mean food energy intake by the US population
based on reported food intake in a national food
consumption survey.(19)
For certain years, annual poundages of some
substances (food additives and ingredients)
produced and used solely for addition to food in
the United States have been compiled as a part
of the National Academy of Sciences (NAS) Survey
of Industry on the Use of Food Additives
(National Research Council, 1972, 1975, 1977,
1982, and 1987(20)).
The reliability and validity of these data depend heavily on
the completeness of the voluntary industry response for a given
substance. A correction factor is applied to
account for under-reporting in the NAS surveys
before the adjusted poundage is determined for
each substance of interest. This factor is
related to the historical percentage of
companies responding to the survey; for the 1982
and 1987 NAS poundage updates the correction factor is 0.6.
Disappearance data cannot be used to estimate
exposure for targeted sub-populations (e.g.,
young children, diabetics, other age/sex groups),
and dietary exposure cannot be expressed on a
body weight basis. Because of the limitations
inherent in this type of data, OPA uses
disappearance data only in conjunction with
exposures obtained using data from different
sources (primarily to check the reasonableness
of an estimate), or when no other data concerning
a substance are available, if it can be inferred that the
substance of interest is widely distributed in the food supply.
FDA conducts a market basket study annually (The
Total Diet Study(21))
to monitor trends in the levels of certain nutrients and contaminants in
representative diets of various age-sex groups.
These diets, compiled from over 200 foods, have
been developed from national food consumption
data. To estimate exposure using data from such
a market basket study, commonly eaten foods
representing the whole diet of the target
population(s) are purchased from the
marketplace, prepared for eating (e.g., cooked),
and then analyzed to determine the concentrations of the substances
of interest in each food. Food consumption data from another
source are then merged with the food composition
data to obtain the desired estimate.
The advantage of the market basket approach is
that chemical analyses are performed directly on
the foods. There is, however, a major drawback
associated with the routine use of this approach
for determining the exposure to food additives
and contaminants in the diet: the total number of
foods analyzed must be limited because of cost
and time restrictions. Additionally, a food that
is unusually high in the component of interest
may not be included in a market basket. Also,
obtaining the distribution of exposures to a
substance over the consumer population is not feasible.
OPA typically estimates exposure by linking food
intakes from surveys to independently
determined concentrations of the substances of
interest. The concentration data used depend on
the nature of the specific exposure assessment.
For a premarket safety evaluation of a food
additive, the proposed levels of the substance in
targeted foods are generally used. For
substances already in the food supply and for
naturally occurring or accidental contaminants,
OPA obtains concentration data from various
sources, such as agency records (FDA, EPA, USDA),
users of the substance, the scientific
literature, or chemical analyses of foods in
which the substance is known to be used or can be found.
OPA evaluates the quality of the concentration
data used for estimating exposure. For
estimating exposure to additives and
contaminants, analytical sampling methodology,
the precision and sensitivity of the method, and
method validation procedures are considered.
Additional considerations are made when estimating exposure to
contaminants. For example, it is important to recognize that a
contaminant is generally not distributed
uniformly in a living organism: its concentration
in plant roots or animal flesh may differ
significantly from that in the leaves of the plant
or the skin of the animal. Therefore, the
concentration of the contaminant in the edible
portion(s) of the organism as prepared for
consumption is estimated or determined before
OPA uses the data to estimate exposure.
Trace levels of materials in foods often fall
below an analytical limit of detection and are
typically reported as "non-detects." A number of
papers have been published discussing the treatment
of data sets containing non-detects for use in estimating
exposures.(22)
Values of zero, one half the limit of detection, the limit of
detection, or some other derived distribution of
values have been assigned to non-detects. OPA
uses all of these methods, selecting the most
appropriate in each case on the basis of the
quality and quantity of data available. To gauge
the effect of non-detect values on an exposure
assessment, the estimation process may be
completed twice: once using zero as the non-detect
concentration to determine the low end of
the estimate range and again using the limit of
detection as the non-detect concentration to
determine the high end of the estimate range. The spread
in this range is useful as a guide in assessing the importance of
non-detect concentration values in a given exposure estimate.
Two factors are required for estimating
exposure to a food substance. The first is the
daily intake of the foods in which the substance
is used or can be found. The second is the
concentration or use level of the substance in
each food. (A simple example of an exposure
estimate is outlined in Exposure
to a Volatile Antimicrobial.) In the early
1970s, data on food intake by individuals were
available from only two nationwide food consumption surveys: the
1965 USDA NFCS and the Market Research Corporation of
America's (MRCA) Menu Census survey. In conjunction with the FDA,
the NAS developed a model for estimating
exposure that combined the MRCA data with the
USDA/NFCS information. The MRCA data provided
information on the frequency of consumption of
foods over a 14-day period; the USDA/NFCS data
provided portion size information. The use of
intakes derived from multiple-day survey of
individuals was considered more representative
of long-term intake than single-day survey-derived estimates. The
relationship of food consumption frequency, portion size, and
substance concentration data to the EDI for a
single individual is captured in the following equation.
where:
OPA typically estimates exposures to substances
that may be consumed by the national population
or a large sub-population. The most useful
exposure information is derived from a distribution of exposures
for the target population, rather than a single exposure figure.
If OPA were assessing the safety of a food containing a
substance that showed toxic effects in pregnant animals,
the distribution of food intakes for women of child-bearing age
would be used for the exposure analysis. For a national
population, OPA is concerned with the potential for high exposure
to food additives or contaminants for individuals who consume
substantial quantities of the food(s) that may
contain these substances. Information on food-intake distributions
provides a means for estimating exposures to components of foods for
the fraction of the population that can be considered "heavy"
consumers of the foods of interest. OPA defines "heavy" consumers as
those individuals who consume the food at or
above the 90th percentile of the food intake distribution.
Chronic Intake
For the premarket evaluation of the safety of a
food additive or to assess the risk associated
with long-term exposure to a contaminant, OPA
evaluates data concerned with lifetime (chronic)
exposures to the substance. Food intake data derived from a
multiple-day food consumption survey are used. OPA assumes
that consuming a variety of foods over a multi-day period
reflects the probable eating pattern of a population over a
long period of time. The concentration values for the
substance are chosen to reflect the levels likely to be found
over time. A regulatory upper use limit could be
used for a food additive that is expected to be
consumed at a relatively constant level over
time. OPA may decide to use an upper limit in a
specific exposure assessment because average
levels might underestimate the intakes of heavy
consumers who consume the treated product
frequently, or have a preference for a brand
treated with the highest concentration. On the
other hand, for a persistent contaminant such as
lead or heavy metals, OPA would use an
analytically determined mean concentration,
including non-detects, to reflect probable exposure conditions.
Acute Intake
OPA must also focus on very short-term, or even single, exposures,
especially for contaminants associated with acute toxic effects. To
estimate exposure in these cases, food intakes
from single eating occasions or from one-day
intakes (sometimes referred to as person-day
intakes) would be used. Using a substance concentration from the
high end of the distribution of measured levels would ensure
that the risk assessment associated with the
exposure assessment would be conservative for a
heavy consumer of food containing the substance.
When food intake data are not available, or are
known to be underreported in food intake surveys
(e.g., alcoholic beverages), eating scenarios may be developed
for use in estimating exposure (an eating scenario is illustrated
in the example Special
Cases - Dietary Scenarios.)
The EPA guidelines for exposure assessment,
published in 1992, concisely state: "Exposure
assessments are done for a variety of purposes,
and for that reason, cannot be easily regimented
into a set format or protocol. Each assessment, however,
uses a similar set of planning questions, and by addressing these
questions the assessor will be better able to decide what is needed
to perform the assessment and how to obtain and use the information
required."(25)
After defining the nature of the risk associated
with the substance under consideration, the sub-populations at risk,
and the food in which the substance may be found, information on the
intakes of the foods affected and the concentration of the substance
in each of those foods is compiled. At this point, the manner in
which this information is used becomes
paramount. Although the model for estimating
exposure requires that incremental exposure to
the substance from each food be summed to
determine the total exposure to the substance,
in reality this operation may be very different
depending on whether raw or summary food intake
data are available.(26)
When the raw data from a food consumption
survey are available, reported food intakes for
each individual in the survey can be combined
with substance concentrations to estimate individual exposure
to the substance. A distribution of the exposures for a target
sub-population can then be derived and used in the
risk assessment. OPA uses this methodology
whenever possible because estimates of
exposure obtained this way are more accurate
than those obtained with summary intake data and
should be considered the "state of the art." The
proprietary software available to OPA for
accessing the raw data from the 1987-88 NFCS, and
the 1989-90, 1990-91, and 1991-92 CFSII's permits such an approach.
When only summary food intake survey data are
available, assumptions must be made about how to
combine exposures from the intake of the
individual foods (or food groupings) containing the substance. An
example of food intake summary data is presented in Table 1.
If the concentration of substance x is 10 µg/g in
food A and 25 µg/g in food B, the exposure to x
from the consumption of each food is shown in Table 2 below.
The mean and 90th percentile exposures to
substance x from the consumption of foods A and
B cannot be taken from Table 2. The eaters-only
exposure from food A in Table 2 cannot be added
to that from food B because the 65% of the population that eats
food A is not identical to the 23% of the population that eats
food B. To sum individual exposures, the exposures must be
placed in terms of the total sample. Total sample
mean exposures can be summed. In the above
example, the total sample mean exposure to
substance x (provided it is only found in foods A
and B) would be 249 µg/p/d (65% of 250 plus 23% of 375).
To convert this total sample mean exposure to an
eaters-only exposure, the percentage of the
population that is consuming either foods A or B
(or both) must be determined. The percentage of
eaters of A or B (or both) in this example lies
between 65 and 88%, as shown in Figure 1.
In case a., the population of eaters of food A and
the population of eaters of food B are different.
Hence, the percentage of the total population
that eats either Food A or B is 88 (65% + 23%).
This scenario represents the eaters of "either-or" type foods, e.g.,
coffee or tea, soda or diet soda, etc. In case b., a consumer's
choice of one food, e.g., lasagna or chocolate ice cream, is
unrelated to the choice of another food. The
overlap of the two populations is a statistical
sampling equal to the product of the two percentages of eaters
(0.65 x 0.23 = 0.15).(27)
Hence, the percentage of the total population
that eats A or B (or both) is
73 (88%(28) - eaters
of A and B (15%)). In case c., a consumer who has
chosen to eat food A will also eat food B. For
example, dieters might use packets of artificial
sweetener (food B) and drink diet soft drinks
(food A). The percentage of eaters of A or B in case c. would
be 65%.(29)
The size of the eating population must be
calculated on a case-by-case basis. Case a. is
less likely to occur when many foods contain the
substance of interest because almost everyone
will consume one or the other of the treated (or contaminated) foods.
The most conservative estimates of exposure are made by assuming the
lowest possible eating population (case c.). In
most cases, assuming the statistical blend (case
b., above) should provide a reasonable estimate
of the size of the eating population and hence a
reasonable estimate of exposure (see example
Multiple-Use Additives - Probable
Exposure for an Emulsifier).
Upper percentile estimates
OPA estimates upper percentile exposure to
substances in the diet to account for individuals
who are considered heavy consumers of specific
foods (the 90th, 95th and 97.5th percentile
exposures are used by various regulatory bodies
in the world; OPA typically uses the 90th
percentile). Approaches for estimating upper
percentile dietary exposure from summary intake data on
individual foods or food groupings are discussed in this section.
An intake estimate for a specific percentile for
each food represents the intake of that food for
a specific population. Thus, summation of these
percentile exposures from individual foods is
incorrect and should be avoided, particularly in
estimates for high consumption groups (e.g., the
intake for corn at the 90th percentile and the
intake for pizza at the 90th percentile would
almost certainly not be representative of any
one consumer).
Examination of food frequency and other types of
food consumption surveys conducted in the
United States, shows that intake at the 90th
percentile for most commonly-consumed foods is
roughly 2 times the mean intake for that food,
and intake at the 95th percentile is roughly 4
times the mean intake. Thus, a crude
approximation of intake at the 90th percentile of
a substance can be obtained by doubling the calculated mean
intake and at the 95th percentile by quadrupling the mean.
Computer-based Monte Carlo simulations have
been used by OPA to calculate specific percentile
intakes for substances using summary
data.(30)
These simulations are used to evaluate models in
which one or more inputs (here, food intakes and
substance concentrations) can be defined by a
distribution of values. Rather than using a
single value (e.g., a mean or 90th percentile food
intake) for such an input, a computerized Monte-Carlo simulation
selects a value at random from the distribution of possible
values for the input, uses that value to calculate the
outcome of the model, stores the result, and then repeats the
procedure a pre-determined number of times
(iterations), using new values of the input taken
from the distribution for each iteration. The
resulting output from this procedure is a range
of possible outcomes for the model. A
probability distribution function is prepared
from the range. An exposure at a designated
percentile may be obtained directly from the
distribution function.(31)
Because Monte Carlo modeling is a probabilistic technique that can
use all the available food intake and concentration data, more
accurate estimates at upper percentiles than those obtained using
point values will result (see results in the example
Multiple-Use Additives -
Probable Exposure for an Emulsifier).
The strength of the Monte Carlo modeling technique is that it
allows for a more realistic estimation of exposure for the mean
and for given centiles of a population of eaters when more than
one food source for a substance is available than does
summing individual food exposures from summary data. When modeling
exposure with a Monte Carlo simulation, food intakes, use levels
(or concentrations), and eater/non-eater variables can be accessed
as distributions (or "Yes/No toggles" in the case of
eater/non-eater), using the complete range of
available information. Estimates of exposure
are derived through Monte Carlo modeling for
substances that are used or found in a number of foods; consumers
food choices may be considered through the use of correlation
functions. As an example, it is possible to test
the scenario in which all peanut butter eaters
are assumed to be jelly eaters (a reasonable
assumption for the subpopulation of young children).
Go to the examples for this document Hypertext updated by dms/hrw 2004-JAN-06 INTRODUCTION
Direct vs. Indirect Food Additives
Direct Additives and Chemical Contaminants
SOURCES OF DATA FOR ESTIMATING EXPOSURE
Food consumption surveys
Food/component disappearance data
Market basket studies
Substance concentration data
Non-detects
MODELING EXPOSURE ANALYSIS
Background
F = Total no. of foods in which x can be found
Freqf = No. of eating occasions for food f over N survey days
Portf = Average portion size for food f
Concxf = Concentration of the substance x in the food f
N = No. of survey days
Food intake distributions
Types of food intake estimates
Statistical approaches to data analysis
Table 1
Percent eaters
Food Intake (Eaters-only)
mean (g/p/d)
90th percentile (g/p/d)
Food A 65 25 45
Food B 23 15 35
Table 2
Concentration (µg/g)
Exposure to X (Eaters-only)
mean (µg/p/d)
90th percentile (µg/p/d)
Food A 10 250 450
Food B 25 375 875 Figure 1
Effect of Overlap of Eater Sub-Populations
on Total Eater Population
a.) No overlap - Largest eater population
b.) Partial (statistical) overlap
c.) Total overlap - Smallest eater population * Office of Premarket Approval, Center for Food Safety and
Applied Nutrition (HFS-200), Food and Drug Administration,
200 C St., SW., Washington, DC 20204 (See updated contact information)
Go to the footnotes for this document
Food Ingredients and Packaging
|
Guidance for Submitting Petitions
Foods Home
|
FDA Home
|
Search/Subject Index
|
Disclaimers & Privacy Policy
|
Accessibility/Help