244
P. Volarath et al.
a positive result suggests that further examinations, such as serum screening studies,
may be needed. It should be noted that the allergenicity assessment uses a weight-ofevidence framework that not only utilizes the AA sequence homology analysis, but
also considers many other factors such as the source and stability of the new protein,
and serum cross-activity test (if necessary) [58].
12.2.4 OFAS’s Food Ingredient Knowledgebase CERES
In addition to the in silico methods described above, the development of databases for
storage and organization of data to support the in silico activities and results from the
safety assessment of food ingredients are also important. At OFAS, a food ingredient
knowledgebase called CERES is available in-house to the review scientists to enable
efficient utilization of available chemical and toxicological data while performing
safety assessments of food ingredients. The CERES knowledgebase is comprised of
data from several sources. One of these sources is the chemical and toxicological
data submitted to OFAS in industry submissions, such as food additive petitions and
FCNs, that provide information to support the authorization of new or expanded uses
of food additives. These industry submissions typically contain chemical, toxicological, environmental, microbiological, and other data supporting the safety assessment
of a new food additive. From these submissions, the Chemical Abstract Service Registration Numbers (CASRN), chemical names, submission type, submission number,
chemicals’ use types/functions, etc., are abstracted into CERES, allowing the connection of the chemical and toxicological data in CERES to the original dossiers
submitted to FDA. The toxicity data included in the submissions are also carefully reviewed and abstracted into CERES by an internally trained data harvesting
team. The harvested toxicity data includes in vitro assays (e.g., bacterial mutagenesis, in vitro chromosome aberration, in vitro micronucleus, in vitro mammalian
mutagenesis, and cytotoxicity) and in vivo assays (e.g., acute, sub-chronic, chronic,
reproductive, developmental, reproductive-developmental, multi-general reproductive, carcinogenicity, and in vivo chromosome aberration). The most important information stored in the CERES knowledgebase is the institutional knowledge generated
during the safety evaluations of those submissions, which includes the reviewers’
evaluations of and conclusions on the toxicity data submitted regarding the food
substances and its impurities. Lastly, the knowledgebase contains the subsumed data
from the Priority-Based Assessment of Food Additive (PAFA) database. PAFA is
the FDA’s legacy database that contained chemical and detailed toxicological (oral,
acute, and genetic toxicity) data on approximately 1700 direct food additives regulated in the USA since the 1970s [59]. Other information such as the annual usage in
food, estimated daily U.S. dietary intake and the Joint Committee on Food Additives
Allowable Daily Intake Values, and the FDA Redbook structure categories of the
chemicals are also contained within the database. A full list of the PAFA data fields
can be found in Benz et al. 1991 [59]. The PAFA system became inactive in 2010,
P. Volarath et al.
a positive result suggests that further examinations, such as serum screening studies,
may be needed. It should be noted that the allergenicity assessment uses a weight-ofevidence framework that not only utilizes the AA sequence homology analysis, but
also considers many other factors such as the source and stability of the new protein,
and serum cross-activity test (if necessary) [58].
12.2.4 OFAS’s Food Ingredient Knowledgebase CERES
In addition to the in silico methods described above, the development of databases for
storage and organization of data to support the in silico activities and results from the
safety assessment of food ingredients are also important. At OFAS, a food ingredient
knowledgebase called CERES is available in-house to the review scientists to enable
efficient utilization of available chemical and toxicological data while performing
safety assessments of food ingredients. The CERES knowledgebase is comprised of
data from several sources. One of these sources is the chemical and toxicological
data submitted to OFAS in industry submissions, such as food additive petitions and
FCNs, that provide information to support the authorization of new or expanded uses
of food additives. These industry submissions typically contain chemical, toxicological, environmental, microbiological, and other data supporting the safety assessment
of a new food additive. From these submissions, the Chemical Abstract Service Registration Numbers (CASRN), chemical names, submission type, submission number,
chemicals’ use types/functions, etc., are abstracted into CERES, allowing the connection of the chemical and toxicological data in CERES to the original dossiers
submitted to FDA. The toxicity data included in the submissions are also carefully reviewed and abstracted into CERES by an internally trained data harvesting
team. The harvested toxicity data includes in vitro assays (e.g., bacterial mutagenesis, in vitro chromosome aberration, in vitro micronucleus, in vitro mammalian
mutagenesis, and cytotoxicity) and in vivo assays (e.g., acute, sub-chronic, chronic,
reproductive, developmental, reproductive-developmental, multi-general reproductive, carcinogenicity, and in vivo chromosome aberration). The most important information stored in the CERES knowledgebase is the institutional knowledge generated
during the safety evaluations of those submissions, which includes the reviewers’
evaluations of and conclusions on the toxicity data submitted regarding the food
substances and its impurities. Lastly, the knowledgebase contains the subsumed data
from the Priority-Based Assessment of Food Additive (PAFA) database. PAFA is
the FDA’s legacy database that contained chemical and detailed toxicological (oral,
acute, and genetic toxicity) data on approximately 1700 direct food additives regulated in the USA since the 1970s [59]. Other information such as the annual usage in
food, estimated daily U.S. dietary intake and the Joint Committee on Food Additives
Allowable Daily Intake Values, and the FDA Redbook structure categories of the
chemicals are also contained within the database. A full list of the PAFA data fields
can be found in Benz et al. 1991 [59]. The PAFA system became inactive in 2010,