The Toxicologist - Society of Toxicology

is required to determine if other reported hepatic adverse reactions associated with
products labelled as containing BC may be related to mis-identified herbs present
in the implicated products, or if other factors may be responsible.
2440 SAFETY ASSESSMENT OF FOOD INGREDIENTS
ORIGINATING FROM GENETICALLY MODIFIED
BACTERIA.
L. Dolan and G. A. Burdock. Burdock Group, Orlando, FL.
The FDA has developed guidance for data that should be included in food additive
petitions and generally recognized as safe (GRAS) notifications for enzyme preparations.
While this guidance includes some information about additional requirements
that are necessary for enzyme preparations from genetically modified organisms
(GMOs), a specific guidance document delineating all steps and tests that are
necessary for the safety assessment of enzyme preparations from genetically modified
bacteria (or products derived from use of these enzymes) has not been created.
The purpose of this poster is to systematically describe issues that should be addressed
to obtain approval of food ingredients derived from genetically modified
bacteria (GMB), and tests that may be performed to address these issues. Several
GMB-derived enzymes (or products derived from them) that have undergone the
series of tests mentioned in this abstract have received generally recognized as safe
(GRAS) status. First and foremost, the source and production strains of the bacteria
should be nonpathogenic and have a history of safe use. The vector should contain
DNA sequences that will precisely code for enzyme production. Specifications
for materials produced from the GMB should include limits for antibiotics (if used
in production), pathogenic bacteria, and bacterial endotoxins. Tests must demonstrate
that that: 1) the sequences of the synthesized and native enzymes are identical;
2) the synthesized enzyme is not allergenic; and 3) the enzyme (or the ingredient
produced from the enzyme) is not contaminated with bacteria, DNA, or toxins.
Conventional toxicity tests that are required for new food ingredients also should
be performed in order to determine a safe level of exposure to the ingredient synthesized
by the GMB. By performing the analyses and tests mentioned above, the
producer should be able to demonstrate that the GMB-synthesized food ingredient
would be as safe as the same ingredient produced by a conventional method.
2441 APPROACH FOR DETERMINING IF DATA ON
HETEROLOGOUS STRAINS OF SIMILAR SPECIES
WOULD SUPPORT THE SAFETY OF A PARTICULAR
STRAIN WHERE DATA ARE LACKING.
S. Choi, K. Howse and A. Roberts. Cantox Health Sciences International,
Mississauga, ON, Canada. Sponsor: L. Haighton.
When attempting to assess the safety of a particular strain, there are often limited
toxicological data for the strain of interest. In these cases, data on other strains
within the same species may provide important insight into the safety of the species
as a whole. We can gain insight into toxigenic, pathogenic, or allergenic properties
associated with the species. This information is useful in determining if the strain is
derived from a safe lineage. However, in order to use such data, it first must be determined
whether the strains are sufficiently similar from a toxicological point of
view. We propose a method for determining when a surrogate strain can be used to
support the safety of another strain of interest. The first step is to analyze the genetic
similarity of the strains (i.e., DNA-relatedness) and determine sequence differences
and the genes within these regions. Differing sequences must be analyzed
to determine if there are resulting changes at the phenotypic level. These type of
data are useful in determining whether the strains may differ in the expression of
deleterious products. The second step is the consideration of the composition of the
resulting product; the major constituents of the end products should be compared
to ensure that they are sufficiently similar between strains. Third, exposure of the
surrogate strain must cover the expected exposure of the strain in question. Finally,
potential properties of the surrogate strain, such as expression of antibiotic resistance
genes, toxins, or allergens, must be assessed for safety. Using the results from
the above analyses, it can be determined if data from a surrogate strain support the
safety of a particular strain of interest.
2442 COMPOSITION OF MULTIPLE LOTS OF EVENING
PRIMROSE OIL COMPARED WITH CORN OIL.
T. Cristy 1 , S. Graves 1 , V. G. Robinson 2 and C. Smith 2 . 1 Battelle Memorial
Institute, Columbus, OH and 2 National Institute of Environmental Health Sciences,
Research Triangle Park, NC.
Evening Primrose Oil (EPO) has been selected for testing on the National
Toxicology Program due to widespread use as a dietary supplement and the lack of
adequate toxicological data. Four lots of EPO and one lot of corn oil were procured
524 SOT 2011 ANNUAL MEETING
from different vendors. They were analyzed for fatty acids by gas chromatography
following saponification and methylation, peroxides by titration, and sterols and
tocopherols by gas chromatography. All lots of EPO consisted of 67 to 71% linoleic
acid, 8 to 9% γ-linolenic acid, 6% palmitic acid, 5% oleic acid, 2% stearic acid, and
less than 1% each of α-linolenic, eicosenoic, and arachidic acids. The composition
of the corn oil was similar with 53% linoleic acid, 10% palmitic acid, 24% oleic
acid, 2% stearic acid, and less than 1 percent each of α-linolenic, γ-linolenic,
eicosenoic, and arachidic acids. The only sterol or tocopherol present above 0.1 percent
in the oils was β-sitosterol, which was present at approximately 0.3 percent in
the EPOs and 0.2 percent in corn oil. Stigmastanol, stigmasterol, campesterol, αtocopherol,
Δ-tocopherol, and γ-tocopherol were all detected, but less than 0.1 percent.
Three of the four lots of EPO had peroxide numbers (10 – 20 meq/kg) higher
than the fourth (1 meq/kg), indicating they had undergone more oxidation during
storage. This work was supported by NTP Contract N01-ES-55551.
2443 MINERAL CONTENT OF COMMONLY INGESTED
BEVERAGES AND BOREHOLE WATER IN NNEWI,
NIGERIA.
O. Orisakwe 1 , H. Enuh 2 , N. Ekwo 2 , V. Obidile 2 and A. Ibekie 2 . 1 University of
Port Harcourt, Rivers State, Port Harcourt, Nigeria and 2 Nnamdi Azikiwe University,
Nnewi, Nigeria.
Epidemiological studies have examined relationships between exposure to trace elements
and minerals in dinking water/beverages and the occurrence of disease, including
reproductive outcome. Because water-bone minerals are in ionic form and
are easily absorbed by the gastrointestinal tract, it has been suggested that drinking
water may be an important source of mineral intake. Using a market basket method
we examined the chemical status of commonly ingested beverages including borehole
(ground water) in Nnewi, Nigeria with respect to K+, Na+, Ca2+, Mg2+ and
pH values and hence to ascertain the nutrient value of these elements in water using
Flame photometry.The pH ranged from 6.27-6.88 in Otolo, 6.40- 7.30 in Uruagu,
6.68-7.50 in Nnewiichi and 6.01-6.69. Na+ and K+(mg/dl) ranged from 2.30-
13.30 and 3.51-6.24 respectively. Chivita Orange Juice had highest level 828mg/dl
of Na+ and SQUAD 5 had 780.0 mg/dl of K+. Ca2+ and Mg2+ were highest in
Vita Vita Apple Drink (113.6mg/dl) and Maltina Sip-it (34.51mg/dl) respectively.
Imported beverages had minerals ranged from 46-690 mg/dl (Na+), 19.5-
780mg/dl (K+), 40.8-136.4mg/dl (Ca2+) and 12.64 – 23.57mg/dl of Mg2+ . The
results suggest that borehole water and beverages may be important dietary sources
of Ca2+, Mg2+, Na+ and K+. We may conclude that borehole water and beverages
may be important dietary sources of Ca2+, Mg2+, Na+ and K+. Drinking water
sources and beverages available to the local population in Nnewi, South Eastern
Nigeria especially Nnewi may contain clinically important levels of these of minerals.
This research was made possible by funding from The Africa Education
Initiative (www.nef3.org)
2444 OVERVIEW.
W. Klimecki. University of Arizona, Tucson, AZ.
Autophagy is a cellular process by which organelles, cytoplasm, and specific proteins
are delivered to the lysosome where they are degraded. Autophagy has been
described for at least four decades, but the scope and the importance of this programmed
cellular response have only recently come into focus, heralded by an exponential
increase in autophagy publications. One clear message that is emerging
from these early studies of autophagy is its relevance to the field of toxicology.
Diverse xenobiotics are capable of perturbing autophagy, with effects ranging from
autophagy induction to complete inhibition. The functional consequences of these
perturbations are complex: in some instances autophagy induction is cytoprotective,
however in some instances its induction is a cell death pathway. The significance
of autophagy to toxicology is underscored by its fundamental role in biology.
It is an ancient process. Many autophagy pathway members were initially characterized
in Saccharomyces cerevisiae, where autophagy can be induced by nutrient
deprivation. In Drosophila melanogaster autophagy plays a critical role in embryonic
development, responding to steroid signaling pathways by executing programmed
cell death. In species from Caenorhabditis elegans to Homo sapiens autophagy
plays a key role in mitochondrial dynamics and in clearing damaged
mitochondria. In the immune system autophagy is critical to antigen presentation,
the development of regulatory and effector functions, and the acquisition of tolerance.
Thus, autophagy plays an evolutionarily conserved role in multiple biological
processes. The ability of environmental stress and xenobiotics such as inorganic arsenic
to modulate autophagy points to the need for an appreciation of this longknown,
but poorly understood, pathway in toxicology.