which are available from the agency’s
website. However, it is important to
keep in mind that while the guidance
reflects the agency’s current thinking on
the subject, it is not binding on industry
or FDA, and a petitioner is free to use
an alternative approach that satisfies the
requirements of the applicable statutes
and regulations.
A color additive petition should be
submitted to FDA’s
Office of Food Additive Safety (OFAS) for
processing and review.
Upon receipt of the
petition, FDA will
form a review team
consisting of chemists,
toxicologists and other
scientists who will
conduct an initial review. FDA will notify
the petitioner within
15 days whether, based
on the team’s assessment, the petition
can be filed. If the petition is accepted
for filing, the agency will publish a notice of filing in the Federal Register containing a brief description of the scope
of the petition and information regarding the petitioner. If the petition is not
accepted for filing, FDA will inform the
petitioner of the reasons for not filing it
and the petitioner will have an opportunity to address the deficiencies. After
the petition is filed, FDA will begin its
detailed review.
The review of a color additive peti-
tion is managed by the OFAS. OFAS
scientists frequently work with scien-
tists in FDA’s Office of Cosmetics and
Colors in the review of color additive
petitions. A chemistry reviewer as-
signed to the petition is responsible for
establishing the identity of the color
additive, including the components
of the color additive and possible
impurities. The chemistry reviewer
also is responsible for determining
specifications of identity and purity to
ensure the color additive’s safe use. The
chemistry reviewer considers whether
the submitted analytical methods are
adequate to identify and quantify the
color additive, its components and im-
purities to ensure compliance with the
proposed specifications, and to identify
and quantify the color additive under
its intended condition of use to ensure
the safety of the color additive. In addi-
tion, the chemistry reviewer determines
whether the use level corresponds to an
amount consistent with CGMPs. The
same or another chemistry reviewer is
responsible for esti-
mating the likely con-
sumer exposure to the
color additive at the
petitioned-use level.
A toxicology reviewer
is responsible for the
review of the available
toxicity information
to determine the
information that is
relevant to the safety
decision for the color
additive and whether
the information provided by the peti-
tioner and other available information
demonstrate that the proposed use of
the color additive is safe. Finally, an
environmental reviewer is responsible
for assessing whether the proposed ac-
tion may significantly affect the quality
of the human environment.
Exposure Level as a Factor
One critical aspect of FDA’s review is
the estimation of consumer exposure to
the color additive at the petitioned-use
level. Various approaches for estimating
consumer exposure may be used. However, no matter which method is used,
it must produce a suitably conservative
estimate that provides an adequate margin of safety. For food use, the typical
approach for exposure assessments employs information from food consumption surveys, combined with maximum
concentrations of the color additive
in foods, to arrive at a range of exposures across the consumer population.
Exposure is usually estimated for the
mean and 90th percentile of consumers
age two or older, as well as for relevant
subpopulation groups (e.g., children).
However, other approaches may be
appropriate to estimate exposure. For
example, disappearance (i.e., into the
food supply) or production poundage
data may be sufficient in circumstances
where a color additive is used in a wide
variety of foods such that it will be pres-
ent in the diet of a large proportion of
the population. The exposure estimate
for an ingested color additive is referred
to as the estimated daily intake (EDI).
FDA encourages petitioners to discuss
the appropriate approach to estimating
exposure to color additives from these
uses when preparing a petition.
Another critical aspect of FDA’s
review is the determination of whether
consumer exposure to the color additive at the petitioned-use level is safe.
FDA has published toxicology guidance
known as the “Redbook” (Toxicological
Principles for the Safety Assessment of Direct
Food Additives and Color Additives Used in
Food) for determining the relevant safety
data needed to address the anticipated
consumer exposure to a color additive
petitioned for use in foods. The testing
paradigm in the Redbook uses a tiered
approach based on the structure of the
compound and expected exposure. Essentially, the higher the exposure, the
more safety data are needed to support
that level of exposure. The Redbook can
serve as an initial reference to petitioners for safety studies of color additives
intended for use in foods. However,
FDA strongly recommends that petitioners consult with the agency before
conducting any safety studies.
For color additives intended for use
in foods, the toxicology data set would
generally be analyzed to determine an
acceptable intake level, based on the
most appropriate endpoint in the most
sensitive species. This endpoint is typically based on either a no-observable-adverse-effect level or a benchmark dose
level. Safety factors are then typically
applied to ensure an adequate margin
of safety, considering inter- and intra-species variations and any limitations
on the data set. The result is either the
establishment of an acceptable daily
intake (ADI) or an acceptable level of
exposure. If the EDI is at or below the
REGULATORY REPORT
“Color additives are
used to affect or
offset color loss, or
to correct natural
variations in color.”