The Toxicologist - Society of Toxicology

centration(μg/g) were: 5.1–95.3; 2.4–4.8 and 0.1–1.6 for Cu, Cr and Pb, respectively.
The statistical analysis shows differences between the average and median values
for Cu data, and high dispersion for Cu and Pb(head, supermarket). The results
were compared with the existing mexican regulations for heavy metals in food.
According to the NOM-051-SCFI/SSA1-2010, the reference nutrition values(daily
suggested intake, mg/day) are set for Cu and Cr as: 0.65 and 0.022, respectively.
The maximum, average and median values obtained for Cu and Cr are above the
regulations, regarding the consumer exposure. And maximum values for Pb, exceeds
the recommendations from NOM-029-SSA1-1993 and NOM-129-SSA1-
1995(maximum limit value:1.0mg/kg Pb).
2435 DETERMINATION OF TOXIN CONTAMINATION IN
DIETARY SUPPLEMENTS MARKETED IN GERMANY.
A. H. Heussner 1 , J. Fastner 2, 1 and D. R. Dietrich 1 . 1 Human & Environmental
Toxicology, University of Konstanz, Konstanz, Germany and 2 Section II 3.3 -
Drinking-water resources and treatment, Federal Environmental Agency, Berlin,
Germany.
Blue-green algae (Spirulina sp., Aphanizomenon flos-aquae) as well as Chlorella sp.
are commonly used as dietary supplements. Whereas Spirulina and Chlorella
species are mostly produced in aquaculture, A. flos aquae is naturally grown and
harvested from Upper Klamath Lake, Oregon, USA. Especially cyanobacterial
products have given cause for serious concern in the past, especially as adverse
health effects were reported by consumers repeatedly and marketed products appeared
to be contaminated with toxins. The aim of the current study was to determine
the type and level of toxin contamination in dietary supplement products
marketed in Germany. Thirteen products from the German market (bought randomly
in 2010) and consisting of A. flos-aquae, Spirulina and Chlorella products
marketed under varying brands, were analyzed for concentration levels of microcystins
(MCs), nodularins, saxitoxins (PSPs), anatoxin-a and cylindrospermopsin.
Additionally, five products tested previously (2003-2008) were re-analyzed for
comparison. Product samples were extracted (liquid extraction) and submitted to a
cytotoxicity assay (MTT) as well as to various toxin analyses: (1) Phosphatase inhibition
assay (PPIA), (2) ELISA and (3) LC-MS/MS. All extracts were cytotoxic in
the epithelial cells employed, thus potentially explaining the diarrhea often reported
in conjunction with the consumption of these dietary supplements. All of
the A. flos-aquae products tested positive for MCs, while all samples were negative
for the other toxins. The contamination levels of the MC-positive samples were either
below or around the guideline value of 1 μg MC-LR equivalents/g d.w. of the
Oregon Department of Health. However, in view of the fact that MC-LR was classified
as a probable human carcinogen (2B) and the fact that MCs were demonstrated
to potentially contribute to the onset and progression of neurodegenerative
diseases the observed MC contamination levels are clearly of concern.
2436 SPIRULINA: TRANSITION FROM POOR MAN’S FOOD
TO A DIETARY SUPPLEMENT.
J. C. Griffiths, G. I. Giancaspro and N. Sarma. Documentary Standards, U.S.
Pharmacopeia, Rockville, MD.
Cyanobacterial organisms (commonly known as blue-green algae) had and still
have a long history of use as regional food across several continents. Arthrospira
platensis a.k.a Spirulina platensis and A. maxima a.k.a. S. maxima have recently
gained widespread and extensive use as dietary supplements due to their high levels
of quality protein with a complete array of essential amino acids, coupled with high
levels of minerals, vitamins, and fatty acids such as gamma-linolenic, docosahexanoic
and arachidonic. Because much of the commercial spirulina is still obtained
from open tropical and subtropical lakes and ponds, and the principal growers are
located in Southeast Asia and Central/South America, the resulting mass harvesting
has brought about issues of contamination with other species of Cyanobacteria.
This work reviews the toxicological concern from contamination with microcystinproducing
non-Spirulina genera (such as Microcystis and Aphanizomenon), the
issue of quality control for spirulina dietary supplements, and the safety evaluation
from US Pharmacopeia for development of a spirulina quality monograph.
2437 FIFTY YEARS OF CHANGE: FATE AND FORTUNE OF
SELENIUM AND MERCURY.
J. C. Griffiths 1 , S. A. Jordan 2 and T. L. Cecil 1 . 1 United States Pharmacopeia,
Rockville, MD and 2 Health Canada, Ottawa, ON, Canada.
Fifty years ago, salts of the elements Selenium (Se, At. No. 34) and Mercury (Hg,
At. No. 80) were found within the pages of the United States Pharmacopeia (USP)
as bona fide pharmaceuticals…and in current editions they still are…but with a sig-
nificant reversal of fortunes. In 1961 selenium sulfide was a presumed toxicant and
its pharmacopeial use limited as an external-only anti-seborrheic. At that same
time, there were several mercury-based salts, i.e., mercurous chloride and mercurophylline,
for oral and parenteral administration, primarily as diuretics and cathartics.
Fast forward to 2011…selenium is now an essential element given orally in
such forms as selenomethionine and selenized yeast, and mercury in all forms is a
tightly controlled and limited as a heavy metal impurity. What changed; the elements,
their toxicity, or our understanding? It is obvious the elements did not
change, but the field of toxicology has changed. The scientific understanding of
how and in what fashion these two elements impact their respective targets has developed
- in the case of Hg, central nervous system and the kidneys, in the case of
Se as a trace essential in nutrition via key metabolic enzymes. The benefit:risk assessment
of these elements, when, used for therapeutic purposes has changed over
time. For instance, in the case of mercury, the development of alternative drugs
used for similar indications, which have a much better benefit:risk profile, lead to
the abandonment of this metal for many of its historical uses. Evolution of the scientific
knowledge with regard to the nutritional role of selenium was a factor in its
increased use in therapeutic products.
2438 RISK ASSESSMENT OF CHICORY ROOT EXTRACT AS
A FOOD INGREDIENT.
R. A. Matulka and G. A. Burdock. Burdock Group, Orlando, FL.
The root of the chicory plant (Cichorium intybus L.) has been consumed for centuries
as a medicinal plant and as food, and both the root and extracts of the root
have gained renewed interest for use in food and dietary supplements. Chicory root
extract is obtained by the water extraction of either the raw or from roasted chicory
root. Chicory has been grown commercially in the US and Europe for the production
of extractable inulin, a soluble fiber gaining commercial applications in a variety
of foods and dietary supplements. Additional substances found in the chicory
root extract include fructose oligosaccharides and volatile substances that include
furfural, oxymethylfurfural and 5-hydroxymethyl-2-furfural, as well as acetophenone.
Chicory root extract has been used as a flavor enhancer and flavoring agent in
many food categories, including baked goods, frozen dairy, gelatin puddings, hard
and soft candy, sweet sauces, and alcoholic and nonalcoholic beverages. Per capita
consumption estimates find that chicory root extract is consumed as a food ingredient
at 0.085 mg/kg body weight/day. Water extracts of chicory root may be increasing
consumption as a tea, while use in dietary supplements may be increasing
due to potential effects on inflammation and potential fiber supplement. Acute and
short-term studies conducted on chicory root extract or its constituents indicate a
low level of toxicity. Subchronic (28-day) administration of chicory root extract to
rats indicated no toxicity at up to 1000 mg/kg/day, while higher doses of chicory
extract administered to adult male Swiss mice over a ten-day period resulted in significant
toxicological effects on the reproductive system. Conflicting studies have
been published on the mutagenic potential of chicory root extract, while other research
indicates potential cytotoxicity of chicory root extract components. In humans,
administration of chicory root extract at up to 1800 mg/day was well-tolerated.
In summary, on the basis of the data presented above, consumption of chicory
extract as an added food ingredient is safe at present use levels.
2439 USP COMPENDIAL MONOGRAPHS FOR DIETARY
SUPPLEMENTS: HELPING TO ENSURE PRODUCT
QUALITY—BLACK COHOSH AS A CASE STUDY.
N. D. Sarma 1 , G. I. Giancaspro 1 , M. Sharaf 1 , J. C. Griffiths 1 , S. A. Jordan 2 and
R. J. Marles 2 . 1 United States Pharmacopeia, Rockville, MD and 2 Health Canada,
Ottawa, ON, Canada.
The manufacture of commercial herbal dietary supplements and natural health
products is sometimes plagued with issues of adulteration, contamination, and misidentification.
Black cohosh (BC, Actaea racemosa L., Ranunculaceae) has become a
popular botanical supplement for symptomatic relief during menopause. Recent
studies in the United States and Canada have shown that some commercial products
labelled as containing this plant have not actually contained authentic BC. In
Canada, active pharmacovigilance was able to identify several BC products, linked
to adverse reactions, which did not contain authentic BC. The United States
Pharmacopeia (USP) compendial monograph for BC provides a method to distinguish
between authentic BC and other related plant species if used appropriately
and routinely as part of the supply-chain due diligence. USP monographs for dietary
supplements (including those for BC) are developed with participation from
stakeholders (academic, regulatory and industry subject matter experts) and the analytical
methods are validated for accuracy, precision, specificity, ruggedness and robustness.
The mis-identification of BC shows that public standards from USP provide
an opportunity to ensure the quality of dietary supplements. Further research
SOT 2011 ANNUAL MEETING 523