FCS 308 California State University of Northridge Amanda Grigg
Dana Sutherland Yelena Tkachenko Professor Darmanyan 05/08/2012
ARSENIC: deficiency/toxicity health impact
Slide 2
ARSENIC: Mineral Characteristics Chemical symbol: As A
metalloid, ultratrace essential mineral Atomic # 33, atomic mass
74.92 Concentration: 2 mg/kg (earth crust) Best natural food
sources: seafoods, meats, cereal and grain products, dairy. Natural
chemical forms: crystalline, powder, amorphous or vitreous (glass)
in all rock, soil, water and air. Recommended Intake: 12-25 g
Estimated Dietary Intake:
ARSENIC: Mineral Characteristics Deficiency: impairs methionine
metabolism curtailed growth reduced conception rate increased
neonatal mortality Toxicity: 1mg > anemia, hepatotoxicity; 10mg
> encephalopathy, GI problems. 70mg>fatal GI problems
hyperkeratosis neuropathy delirium cancer Blackfoot disease
(peripheral vascular condition in Taiwan when drinking
arsenic-containing drinking water) Supplements: traditional Chinese
medicine formulas, herbal kelp. (Gropper at al. 2009)
Slide 7
Commercial Supplements Facts Serving Size: One capsule daily
with food Amount of Minerals per serving: Iron390 mcg Iodide400 mcg
Sodium20mg Kelp(whole thallus)660mg
Slide 8
Commercial Supplements Facts According to our research,
although arsenic is not included on the kelp supplement label, kelp
supplements contain arsenic. Kelp supplements are considered an
Arsenic supplement. Amount of Arsenic per serving: 5.61 g Chemical
Form: trivalent arsenic in the form of inorganic arsenious acid
(arsenite), or an organic arsenoxide
Natural Food Equivalent Foods of marine origin are rich in
arsenic. Oysters contain up to 10 g/g of Arsenic One serving of
oysters (6 medium)= 84 g 84g * (10g/g)= 840 g of Arsenic Kelp
supplement contains 5.61 g A serving of 0.561 grams of oysters is
the equivalent to one serving of kelp supplement. (Gropper et. al.,
2009)
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Possible Mechanism of Supplement Absorption Concentration of As
in the Kelp supplement is 5.61 g in one serving; relatively low As
concentration Mechanism of absorption: simple diffusion Most As is
absorbed through the intestinal walls, then transported to the
liver Inorganic As absorption does not depend on concentration, but
rather its lipid solubility (Gropper at al. 2009)
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Health Impact: Potential Arsenic Toxicosis in Herbal Kelp
Article: Case Report: Potential Arsenic Toxicosis Secondary to
Herbal kelp Supplement Authors: Eric Amster, Asheesh Tiwary and
Marc B. Schenker (USC Davis) Journal: Environmental Health
Perspectives Year: 2007 (Amster et al., 2007)
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Health Impact: Potential Arsenic Toxicosis in Herbal Kelp
Introduction: Commercially available herbal kelp supplements may
contain higher levels of arsenic contamination than previously
known. Chronic use of the supplement may lead to manifestation of
arsenic toxicity symptoms. This study was performed in order to
find out if there is a link between both and to inform clinicians
about a potential heavy metal toxicity. Objective: Medicinal use of
dietary herbal supplements can cause inadvertent arsenic toxicosis.
(Amster et al., 2007)
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Health Impact: Potential Arsenic Toxicosis in Herbal Kelp Case
Presentation: 54 year old woman with symptoms of alopecia, memory
loss, fatigue, rash on legs, GI problems, vomiting, later disabled
(USC Davis). Duration of symptoms: october 2002 to october 2003
with progression of worsening Urine sample = 83.6 g/g creatinine
(normal < 50 g/g creatinine). A sample of kelp supplements = 8.5
mg/kg (ppm) arsenic (normal: 0-50g) Consumption of kelp supplement:
2 to 4 pills a day (1 pill contains 41mg kelp, 66mg Ca, 225 g I)
Tests included: MRI, blood count, chemistry panel, thyroid studies,
diet (seafood:less than one serving), water analysis, other
supplements = all normal levels. When discontinued the supplements,
symptoms resolved and arsenic blood and urine levels were
undetectable within few weeks. parts per million, dilute
concentrations of substances. (ex: 1 ppm is equivalent to 1
milligram of something per liter of water (mg/l) or 1 milligram of
something per kilogram soil (mg/kg). (Amster et al., 2007)
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Health Impact: Potential Arsenic Toxicosis in Herbal Kelp
Methods: 9 samples of random kelp supplements (OTC) including 3 of
patients supplements (same brand not the same bottle). None of the
supplements contained information regarding the possibility of
contamination of arsenic Determination of total arsenic by
inductively coupled argon plasma (ICP) using the identical hydride
vapor generation method (demonstrates statistical control for
samples of biological interest and is especially well suited to
analysis of small samples). A 1 g sample is wet washed in a 16 x
150 mm 10 mL volumetric test tube on a programmed heating block
with nitric, sulfuric, and perchloric acids at up to 310 degrees C.
After treatment with hydrochloric acid and potassium iodide,
arsenic is reduced by sodium borohydride to arsine in a simplified
continuous flow manifold. A standard pneumatic nebulizer affects
the gas-liquid separation of AsH3, which is quantified by ICP
atomic emission at 193.756 nm. The instrument detection limit for
the method has been determined to be 0.4 microgram/L. For a 10:1
dilution of a nominal 1 g sample, the detection limit is 4
micrograms/kg and the linear range is up to 4 mg/kg. Recoveries
from 3 matrixes were 99-104%, with a typical RSD of 2%. Analysis:
Random blind-folded manner Outcome Measures: majority of samples
showed detectable arsenic levels (Amster et al., 2007 & Tracy,
1991)
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Health Impact: Potential Arsenic Toxicosis in Herbal Kelp
Results: 8 out of 9 had higher levels (1.59 to 65.5 ppm) than FDA
tolerance level (0.5 to 2 ppm) 1 out of 9 was below the detection
limit (0.010 ppm) 3 patient samples arsenic concentration were
34.8, 2.28, 1.59 ppm. Patients blood arsenic levels on February
2004 were 8g/L (normal) Conclusion: Given the nature of patients
symptoms and tests performed the study showed a causal associations
between her ingestion and symptoms. Majority of kelp supplements
contain higher levels of arsenic Consumers are misinformed and
arent aware of the metal intoxication exposures. Cause of concerns
when consistency varies batch to batch (same brand variability)
Improper labeling of supplements. Concentrations of materials
contained in preparations, expected benefits and side-effects
should be studied, standardized, monitored and accurately labeled.
(Amster et al., 2007)
Slide 17
Health Impact: Drinking-Water Arsenic Exposure Modulates Gene
Expression Article: Drinking-Water Arsenic Exposure Modulates Gene
Expression in Human Lymphocytes from a U.S. Population Authors:
Angeline S. Andrew, David A. Jewell, Rebecca A. Mason, Michael L.
Whitfield, Jason H. Moore, Margaret R. Karagas Journal:
Environmental Health Perspectives Year: 2008 (Andrew et. al.,
2008)
Slide 18
Health Impact: Drinking-Water Arsenic Exposure Modulates Gene
Expression Introduction: Arsenic exposure impairs development and
can lead to cancer, cardiovascular diseases, and diabetes. In the
northeastern, western, and north central regions of the United
States, arsenic levels in drinking-water exceed the maximum
contaminant level of 10ug/L. (Andrew et. al., 2008)
Slide 19
Health Impact: Drinking- Water Arsenic Exposure Modulates Gene
Expression Objectives: The purpose of this study was to research
the effects of arsenic exposure on gene expression. The effects of
arsenic exposure was determined by internal biomarkers at levels
relevant to the United States and populations with similar arsenic
exposure. (Andrew et. al., 2008)
Slide 20
Health Impact: Drinking- Water Arsenic Exposure Modulates Gene
Expression Methods: Subjects: Selection of 21control subjects who
did not have cancer were used in this study. Route of
Adminitration: Oral Doses of Administration: Unregulated private
wells used for drinking-water High Exposure: (n=11) Averaged 32
ug/L (range: 10.4ug/L- 74.7ug/L) Low Exposure: (n=10) Averaged
0.7ug/L (range: 0.0007ug/L- 5.3ug/L) (Andrew et. al., 2008)
Slide 21
Health Impact: Drinking- Water Arsenic Exposure Modulates Gene
Expression Methods continued: Outcome Measures: Subject selection,
gene expression analysis, and biological function analysis were
performed. Analysis of Internal Biomarkers: Toenail clippings, and
urine samples, venous blood sample. (Andrew et. al., 2008)
Slide 22
Health Impact: Drinking- Water Arsenic Exposure Modulates Gene
Expression Results: High arsenic: 82% male, 18% female Low arsenic:
80% male, 20% female The SAM test identified 259 genes that were
significantly different in the high vs. low arsenic exposure
statuses. Defense and immune response pathways had the most
statistically significant level of modified transcripts associated
with arsenic exposure. Arsenic exposure was also associated with an
increase in expression of the killer cell immunoglobin-like
inhibitory receptors (KIR). (Andrew et. al., 2008)
Slide 23
Health Impact: Drinking- Water Arsenic Exposure Modulates Gene
Expression Results continued: 38 genes were identified to be
significantly different in those with high urinary arsenic levels
versus low urinary arsenic levels. A substantial trend was
identified towards increased transcript abundance for PRF1, IL2RB,
and KIR3DL1 with increasing urinary exposure concentration. (Andrew
et. al., 2008)
Slide 24
Health Impact: Drinking- Water Arsenic Exposure Modulates Gene
Expression Conclusion: Gene expression is modulated because of
arsenic exposure. Chronic arsenic exposure modulates immune
function by decreasing defense response genes. (Andrew et. al.,
2008)
Slide 25
Health Impact: Low Level Arsenic Exposure Is Associated with
Poorer Neuropsychological Functioning Title Long-term Low Level
Arsenic Exposure Is Assiciated with Poorer Neuropsychological
Functioning: A Project FRONTIER Study Authors Sid E. OBryant,
Melissa Edwards, Chloe V. Menon, Gordon Gong, & Robert Barber
Journal International Journal of Environmental Research and Public
Health Year 2011 (OBryant et al., 2011)
Slide 26
Health Impact: Low Level Arsenic Exposure Is Associated with
Poorer Neuropsychological Functioning Introduction The health
impact of high-level exposure to arsenic has been well established,
however there is little reasearch conducted that documents the
health impact of prolonged exposure to groundwater arsenic at
levels below the current U.S. standard of 10 g/L. Arsenic exposure
has been associated with an increase in the production of amyloid,
hyperphoshoralation of tau protein, oxidative stress, inflammation,
endothelial cell dysfunction and angiogenesis, all of which have
been linked to cognitive dysfunction and are proposed mechanisms
underlying Alzheimer's disease. Objective The purpose of the
current study was to examine the potential association between
current and long-term arsenic exposure and neuropsychological
functioning in a sample of rural-dwelling adults and elders
(OBryant et al., 2011)
Slide 27
Health Impact: Low Level Arsenic Exposure Is Associated with
Poorer Neuropsychological Functioning Methods Subjects: 434 adults
ages 40 and up (133 male, 301 female) Route of Administration: oral
Doses of Administration: Parmer County: 3.06 g/L (15 year average)
Cochran County: 7.39 g/L (15 year average) Duration of Experiment:
15 years Outcome Measures: Texas Water Development Board (TWDB)
Geographic Information System (GIS) Project FRONTIER Mini-Mental
state Examination (MMSE), Exit Interview (EXIT25), Repeatable
Battery for the Assessment of Neuropsychological Status (BRANS),
Trails Making test (TMT-A & B), and Controlled Oral Word
association Test (COWAT) (OBryant et al., 2011)
Slide 28
Health Impact: Low Level Arsenic Exposure Is Associated with
Poorer Neuropsychological Functioning Results Current estimated
groundwater arsenic exposure level was significantly associated
with poorer scores in language, visuospatial skills and executive
functioning. Long-term low level exposure to arsenic was
significantly associated with poorer scores in global cognition,
visuospatial skills, language skills, processing speed and
immediate memory Conclusion It cannot be concluded that
long-term-low-level arsenic consumption through water is causally
related to poorer cognition from the current data. These finding
were the first direct evidence that low-level arsenic exposure is
associated with poorer neuropsychological functioning among
community- dwelling adults and elders in the U.S. Further research
is needed, but this study provides ample justification for a re-
evaluation of current policy to acceptable groundwater arsenic
levels. (OBryant et al., 2011)
Slide 29
Conclusion Symbol for Arsenic: As Best natural food source:
seafood Recommended Daily Intake: 12-25 g Mechanism of absorption:
simple diffusion Function: formation and utilization of methyl
groups Deficiency: impairs methionine metabolism Toxicity:
Blackfoot Disease Commercial supplement: Kelp
Slide 30
Conclusion As from supplements is associated with various
symptoms that effect health, such as alopecia, memory loss,
fatigue, rash on legs, GI problems, vomiting Gene expression is
modulated because of As exposure and chronic arsenic exposure
modulates immune function by decreasing defense response genes.
Long-term low level exposure to arsenic was significantly
associated with poorer scores in global cognition, visuospatial
skills, language skills, processing speed and immediate memory
Slide 31
References Amster, E., Tiwary, A. & Schenker, M. (2007).
Case Report: Potential arsenic toxicosis secondary to herb kelp
supplement. Environ Health Perspect, 115:606-608.
http://dx.doi.org/10.1289/ehp.9495 Gropper, S., Smith, J &
Groff, J. (2009). Advanced nutrition and human metabolism, 5 th
edition. Belmont, CA: Wadsworth, Cengage Learning. Tracy, M.,
Littlefield, E. & Moller, G. (1991). Continuous flow vapor
generation for inductively coupled argon plasma spectrometric
analysis. Part 2. Arsenic. J Assoc Off Anal Chem 74:516-521. Rose,
M., Lewis, J., Langford, N., Baxter, M., Origgi, S., Barber, M.,
MacBane, S., & Thomas, K. (2007, January 17). Arsenic in
seaweed--forms, concentration and dietary exposure. Retrieved from
http://www.ncbi.nlm.nih.gov/pubmed/17336439http://www.ncbi.nlm.nih.gov/pubmed/17336439
OBryant, S., Edwards, M., Menton, C., Gong, G., & Barber, R.
(2011, March 15). Long-term low-level arsenic exposure is
associated with poorer neurological functioning: a project FRONTIER
study. International journal of Environmental public health, 8,
861-874.
Slide 32
References Andrew, A. S., Jewell, D. A., Mason, R. A.,
Whitfield, M. L., Moore, J. H., & Karagas, M. R. (2008).
Drinking-water arsenic exposure modulates gene expression in human
lymphocytes from a u.s. population. Environmental Health
Perspectives, 116(4), 524-531. Gropper, S. S., Smith, J. L., &
Groff, J. L. (2005). Advanced nutrition and human metabolism. (4
ed., pp. 489-492). Belmont, CA: Thomson Wadsworth.