Food Safety Magazine - October/November 2017

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