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Food Safety: Toxins and Spoilage

John D. Groopman

Edyth H. Schoenrich Professor of Preventive Medicine


Department of Environmental Health and Engineering
Bloomberg School of Public Health
School of Medicine
Whiting School of Engineering
Johns Hopkins University

Case Studies:

Ø Population health and how much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

©Johns Hopkins University 2021


Case Studies:

Ø Population health and how much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

World Population Growth


U.S. 330,084,524; World 7,740,934,100
http://www.census.gov/popclock
accessed 2-01-21

©Johns Hopkins University 2021


21st Century Population Statistics
2020 2050
1 China 1,394,620,713 1 India 1,807,878,574
2 India 1,325,379,910 2 China 1,437,161,948
3 USA 329,959,265 3 USA 420,080,587
4 Indonesia 272,271,879 4 Nigeria 356,544,098
5 Pakistan 233,242,560 5 Indonesia 313,020,428
6 Nigeria 213,269,059 6 Pakistan 294,995,104
7 Brazil 212,939,233 7 Bangladesh 279,955,405
8 Bangladesh 162,065,352 8 Brazil 228,426,737
9 Russia 141,059,244 9 Congo 183,260,098
10 Mexico 128,763,244 10 Mexico 147,907,650

n Note: Data updated 7-1-2020


n Source: U.S. Census Bureau, International Data Base.

©Johns Hopkins University 2021


February 1, 2021

(10 months later)

(480 months later)

United States: 2019 and 2020

©Johns Hopkins University 2021


United States: 2019 and 2020

**
** COVID-19: 435,000

**

**
**

** major diet/food component


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Life Expectancy Baltimore Washington Region

Engagementnetwork.org

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©Johns Hopkins University 2021


Age-Standardized Death Rates per 100,000 in US,
1969-2013

n The age-standardized death rate per 100 000 decreased


from 1278.8 to 729.8 for all causes (42.9% reduction)
n From 156.8 to 36.0 for stroke (77.0% reduction)
n From 520.4 to 169.1 for heart disease (67.5% reduction)
n From 65.1 to 39.2 for unintentional injury (39.8% reduction)
n From 198.6 to 163.1 for cancer (17.9% reduction)
n In contrast, the rate for COPD increased from 21.0 to 42.2
(100.6% increase)

JAMA. 2015;314(16):1731-1739. doi:10.1001/jama.2015.12319

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Cancer Prevention Opportunities to


Reduce Cancer by 50%

Colditz et al. Sci. Trans. Med, 2012

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Obesity and another epidemiologic transition

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Obesity Trends* Among U.S. Adults
BRFSS, 1990
(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

No Data <10% 10%–14%

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Obesity Trends* Among U.S. Adults


BRFSS, 1994
(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

No Data <10% 10%–14% 15%–19%

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©Johns Hopkins University 2021


Obesity Trends* Among U.S. Adults
BRFSS, 1998
(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” woman)

No Data <10% 10%–14% 15%–19% ≥20

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Obesity Trends* Among U.S. Adults


BRFSS, 2002
or ³~
(*BMI ≥30,(*BMI 30, or ~ 30 lbs overweight for 5’4” person)
30 lbs overweight for 5’ 4” woman)

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Source: Behavioral Risk Factor Surveillance System, CDC

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©Johns Hopkins University 2021


Obesity Trends* Among U.S. Adults
BRFSS, 2006
(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

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Obesity Trends* Among U.S. Adults


BRFSS, 2010
(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

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©Johns Hopkins University 2021


Prevalence of Self-Reported Obesity Among U.S. Adults by
State and Territory, BRFSS, 2014

¶Prevalence estim ates reflect BRFSS m ethodological changes started in 2011. These estim ates should not be
com pared to prevalence estim ates before 2011.

*Sam ple size < 50 or the relative standard error (dividing the standard error by the prevalence) ≥ 30% .

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Prevalence of Self-Reported Obesity Among U.S. Adults by


State and Territory, BRFSS, 2018
¶Prevalence estim ates reflect BRFSS m ethodological changes started in 2011. These estim ates should not be
com pared to prevalence estim ates before 2011.

*Sam ple size < 50, the relative standard error (dividing the standard error by the prevalence) ≥ 30% ,
or no data in a specific year.

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©Johns Hopkins University 2021


Prevalence of Self-Reported Obesity Among U.S. Adults by
State and Territory, BRFSS, 2019
¶Prevalence estim ates reflect BRFSS m ethodological changes started in 2011. These estim ates should not be
com pared to prevalence estim ates before 2011.

*Sam ple size < 50, the relative standard error (dividing the standard error by the prevalence) ≥ 30% ,
or no data in a specific year.

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State-specific Prevalence of Obesity Among


U.S. Adults, by Race/Ethnicity, 2017-2019
White non-Hispanic Black non-Hispanic

Hispanic

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©Johns Hopkins University 2021


Morbid Obesity: BMI >35
n Height 70” with weight greater than 270 pounds
n Offensive Line NFL- Avg. Height: 76.75; Avg. Weight:
314.16 lbs
n In 2018 it is estimated that up to 10% of US population is
morbidly (or extremely) obese
n In 2017 there were an estimated 227,000 bariatric
surgeries
n Improvement in Type 2 diabetes and NAFLD

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Case Studies:

Ø Population health and how much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

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©Johns Hopkins University 2021


Water Activity Permitting Growth of
Microorganisms

Group of Microorganisms Minimal aw Value

Many bacteria 0.91


Many yeasts 0.88
Many molds 0.80
Halophillic bacteria 0.75
Osmotic yeasts 0.60

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Water Activity of Various Foods


Food aw
Fresh fruit, vegetables, meat, fish >0.98
Cooked meat, bread 0.95-0.98
Cured meats, cheeses 0.91-0.95
Sausages, syrups 0.87-0.91
Rice, beans, peas 0.80-0.87
Jams, marmalades 0.75-0.80
Candies 0.65-0.75
Dried fruits 0.60-0.65
Dehydrated milk, spices 0.20-0.50

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©Johns Hopkins University 2021


Formal Agriculture, Grains and Mold
emmer
n Cultivation and storage of grains
starting 10,000 years ago led to
issues of mold contamination.
n First insights and ongoing discovery
often comes from veterinary
diseases.
n Emmer (farro), wheat, barley, rye
and oats, expanded from the Middle
East across Europe.
rye
J Agric Food Chem. 2016 Dec 27. doi: 10.1021/acs.jafc.6b04494

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Formal Agriculture, Grains and Mold:


Africa as a case study
n Main diet came from starch from
cassava, sorghum, and millet.
n Over last 65 years a major diet
change to maize (corn) as a staple cassava
grain in Africa.
n Transition to maize has created a
wider source of mycotoxin
contamination in ecosystems.
n Food security and climate
concerns.
Pearl millet
J Agric Food Chem. 2016 Dec 27. doi: 10.1021/acs.jafc.6b04494

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©Johns Hopkins University 2021


Fungal Contaminants in Food
n More than 300 different fungal toxins (mycotoxins) have
been characterized to date.
n Unfavorable conditions such as drought, damage by
insects or mechanical harvesting can increase mycotoxins
during growth, harvest and storage.
n Production occurs over a wide range of moisture content,
relative humidity, and ambient storage temperatures (4-
350C).
n The major crops affected are corn, peanuts, cotton,
wheat, rice, and the processed food from these crops.

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Fumonisins

n Equine leukoencephalomalacia, porcine pulmonary


edema, and human esophageal cancer.
n First isolated in 1988.
n Levels vary yearly, but consistently in the 0.5 to 2-
ppm range in U.S. cornmeal, and have been
reported as high as 150 ppm in corn destined for
human consumption in South Africa

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©Johns Hopkins University 2021


Ochratoxins

n Ochratoxin A has been detected in many food commodities


throughout the world, but is found primarily in grains
(barley, oats, rye, corn and wheat) grown in northern
temperate areas, and results in contamination of breads
and cereal products.

n Most potent kidney carcinogen ever tested in NTP bioassay


over 35 years

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St. Anthony’s Fire


n Ergotism
n Claviceps purpurea
contaminating wheat
and other grains
n Burning sensation,
hallucinations, LSD-
like symptoms
n Salem Witch Trials

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©Johns Hopkins University 2021


Other Mycotoxins
n Zearalenone, in corn, has estrogenic activity
and binds to estrogen receptors.
n Vomitoxin, from molds contaminating wheat.
n Patulin, is produced by molds that may grow
on a variety of foods including fruit, grains and
cheese and occurs in apple juice, apples and
pears with brown rot.

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Aspergillus terreus

Lovastatin
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©Johns Hopkins University 2021


Food Safety Issues

Microbial
Contamination
Food Natural
Additives Food
Toxins

Environmental
Pesticide
Residues Contaminants

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©Johns Hopkins University 2021


cdc.gov/

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E. coli O157:H7

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©Johns Hopkins University 2021


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©Johns Hopkins University 2021


E. coli O157:H7
Has HACCP led to a reduction
in human incidence?

Excretion

Re-colonization

Death Environment

Courtesy of JR Dunn
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Minimal Infective Doses for Some


Pathogens & Parasites

Organism Minimal Dose


Salmonella spp. 104-107
Shigella spp. 101-102
Escherichia coli 106-108
Escherichia coli O157:H7 ~10
Vibrio cholerae 103
Giardia lamblia 101-102 cysts
Cryptosporidium 101 cysts
Hepatitis A virus 1-10 PFU

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©Johns Hopkins University 2021


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Microbial Foodborne Ailments


Pathogen Time Frame for Onset of Symptoms

Camphylobacter 1 to 10 days (usually 3 to 5 days)


Clostridium botulinum 12 to 36 hours
E. coli O157:H7 1 to 10 days (usually 3 to 5 days)
Hepatitis A 1 to 7 weeks (usually 25 days)
Listeria monocytogenes 4 days to several weeks
Salmonella 6 hours to 3 days (average 18 h)
Staphylococcus aureus 2 to 7 hours

** Salmonella produces fever and Staphylococcus does not.

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©Johns Hopkins University 2021


5-minute break:
In the chat box:
n Write down one thing that you just learned
that was most interesting for you.

n Write down one thing that you would like


to know more about.

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Case Studies:

Ø Population health and how much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

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©Johns Hopkins University 2021


Case Studies:

Ø How much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

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©Johns Hopkins University 2021


AFLATOXIN B1

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Aflatoxin factoids

n Discovered in UK ~1960 in moldy, toxic animal feed


n Frequent contaminant of improperly stored food crops
n Produced by Aspergillus flavus (A.flavus toxin = “Aflatoxin”)
n Spores are globally distributed in soil
n Mold grows on food crops after harvest, before drying
n Corn, peanuts, rice, cottonseed
n Some relevant properties
n Highly fluorescent, heat stable
n Lethal to animals at high levels (“Turkey X disease”)
n Carcinogenic to liver of animals when fed at non-toxic levels
n Immunotoxic to animals and humans

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©Johns Hopkins University 2021


Between 25,000 and 155,000 global aflatoxin-
induced liver cancer cases per year

Liu Y, Wu F. (2010). “Global Burden of Aflatoxin-Induced Hepatocellular Carcinoma: A Risk Assessment.”


Environmental Health Perspectives 118:818-824. 53

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U.S. FDA and EU Guidelines for Acceptable Levels of


Aflatoxins in Food and Feed
Action level (ppb) Commodity Species

0.5 (aflatoxin M1)* milk humans


5 - 20.0 any food (peanuts) except milk humans
5 - 20.0 feed all species

Exceptions

100 - 300.0 cottonseed meal used all species


in feed
50 - 300.0 corn finishing beef cattle
50 - 200.0 corn finishing swine
(>100#)
100.0 corn breeding cattle,
swine, and poultry
* Specifically for aflatoxin M1, a toxic metabolite of AFB1 that occurs in milk
and processed to cheese (10 fold concentration)

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©Johns Hopkins University 2021


Top exporters of maize worldwide
(threshold = 1 million MT)

Wu F, Guclu H. Risk Analysis, 2013

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©Johns Hopkins University 2021


Case Studies:

Ø Population health and how much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

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"To enable the Secretary of Agriculture to investigate the


character of food preservatives, coloring matters, and other
substances added to foods, to determine their relation to
digestion and to health, and to establish the principles which
should guide their use."
The Poison Squad

Borax, Salicylic acid, Sulfuric acid,


Sodium benzoate, Formaldehyde

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©Johns Hopkins University 2021


Candy Color
n Red sulfuret (mercury sulfide)
n Verdigris (copper acetate)

n Blue vitriol (copper sulfate)

n Sugar of lead (lead acetate)

n White lead (lead carbonate)

n Scheele’s green (copper arsenite)

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Food Safety Over the Last 100 Years


n Food and Drug Act of 1906: Dr. Harvey Wiley, director of the USDA’s Bureau of
Chemistry, spurred Congress to pass and President Theodore Roosevelt to sign
the 1906 Food and Drug Act. The 1906 Act prohibited the marketing of
adulterated and misbranded food and drugs.
n Federal Food, Drug and Cosmetic Act of 1938: In 1937, nearly 100 people died
after ingesting a product called Elixir Sulfanilamide, which was prepared using
diethylene glycol.
n Although the manufacturer technically violated the 1906 Act because

the product was called an elixir (by definition this is supposed to contain
alcohol, and this product did not), the company’s failure to test the
product for safety and to label the product adequately were not
violations of the law.
n The 1938 Act compelled manufacturers to demonstrate to the FDA the
safety of new drugs…; set tolerances for substances such as pesticides;
extended regulation to color additives and cosmetics.
n Food Additive Amendment of 1958 and Color Additive Amendments of 1960:
These amendments required pre-market approval by the FDA of food
components and color additives not "generally recognized as safe" by the
scientific community. The use of additives that are shown to be carcinogenic in
animals or humans is prohibited.

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©Johns Hopkins University 2021


Case Studies:

Ø Population health and how much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

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Metabolism Heterocyclic Amines

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©Johns Hopkins University 2021


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Snyderwine, 2000

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©Johns Hopkins University 2021


Metabolic Activation of PhIP

CH3
N
NH2
acetyltransferase?
PhIP N N

liver sulfotransferase?
Prostate
CH3
Colon phosphatase?
N
H
N Breast
N OH
N aminoacyl tRNA synthetase?

N-OH-PhIP

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Intake per Day Cancer Risk Estimate

Carcinogenesis 16: 39, 1995.

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©Johns Hopkins University 2021


IARC Classifies Red and Processed Meat as
Group 2A: Probable Human Carcinogen
n Red meat refers to unprocessed mammalian muscle
meat—for example, beef, veal, pork, lamb, mutton,
horse, or goat meat—including minced or frozen meat;
it is usually consumed cooked.
n Processed meat refers to meat that has been
transformed through salting, curing, fermentation,
smoking, or other processes to enhance flavor or
improve preservation. Most processed meats contain
pork or beef, but might also contain other red meats,
poultry, offal (e.g., liver), or meat byproducts such as
blood.
www.thelancet.com/oncology Vol 16 December 2015

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IARC Classifies Red and Processed Meat as


Group 2A: Probable Human Carcinogen
n A meta-analysis of 10 colorectal cancer cohort studies
reported a statistically significant dose–response
relationship, with a 17% increased risk (95% CI 1.05–
1.31) per 100 g per day of red meat and an 18% increase
(95% CI 1·10–1·28) per 50 g per day of processed meat
n Positive associations were seen in cohort studies and
population-based case- control studies and cancers of
the pancreas and the prostate (mainly advanced prostate
cancer), and between consumption of processed meat
and cancer of the stomach.

www.thelancet.com/oncology Vol 16 December 2015

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©Johns Hopkins University 2021


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Case Studies:

Ø Population health and how much do we eat?

Ø Microorganism growth and fungal toxins

Ø Global impact of aflatoxin

Ø Food testing and regulation

Ø In situ production of toxins

Ø Dietary supplements and food fraud

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©Johns Hopkins University 2021


Food Safety Over the Last 100 Years

n Food and Drug Act of 1906:

n Federal Food, Drug and Cosmetic Act of 1938:

n Food Additive Amendment of 1958 and Color


Additive Amendments of 1960:

n Dietary Supplement & Health Act of 1994


(DSHEA):

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Dietary Supplement and Health Act of 1994


(DSHEA)
• Drugs: Intensively regulated by U.S. Food & Drug
Administration (FDA).
• Dietary supplements: Limited regulation by FDA.
– Can only be withdrawn if FDA can prove clear
and present danger
– Unlike drugs, onus is on FDA to prove danger, not manufacturer
to prove safety
– Supplement must pose “a significant or unreasonable risk of
illness or injury” before FDA can take action
• Congress recently added new requirements for certification
of purity of dietary supplements to current law – DSHEA.

Special thanks to Dr. Harold Lieberman

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©Johns Hopkins University 2021


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Dietary Supplement & Health Act of


1994 (DSHEA): Consequences
• Dietary supplements are not subject to pre-market FDA
approval unless they contain a “New Dietary Ingredient”.
• Demonstration of Safety & Efficacy by manufacturer is not
required; but claims are restricted
• Most naturally-occurring substances, except those already
classified as drugs, can be labeled as a dietary supplement.
– For example: ephedra, melatonin
• Clinical trials of supplements are not regulated by the FDA.

• Without “National Standards” that establish safety and


efficacy, what processes for monitoring supplement use and
abuse since ~70% of young adults regularly take a DS or
related product. Special thanks to Dr. Harold Lieberman

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©Johns Hopkins University 2021


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Food Fraud

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©Johns Hopkins University 2021


Food Fraud

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Supplement: Hazard Analysis Critical Control


Point (HACCP): Seven Principles
1 Analyze hazards. Potential hazards associated with a food and measures to
control those hazards are identified, such as a microbe; chemical, or physical.
2 Identify critical control points. These are points in a food's production--from
its raw state through processing and shipping to consumption by the consumer-
-at which the potential hazard can be controlled or eliminated.
3 Establish preventive measures with critical limits for each control point.
For a cooked food, this might include setting the minimum cooking temperature
and time required to ensure the elimination of any harmful microbes.
4 Establish procedures to monitor the critical control points. Such
procedures might include determining how and by whom cooking time and
temperature should be monitored.
5 Establish corrective actions to be taken when monitoring shows that a
critical limit has not been met--for example, reprocessing or disposing of food
if the minimum cooking temperature is not met.
6 Establish procedures to verify that the system is working properly--for
example, testing time-and-temperature recording devices to verify that a
cooking unit is working properly.
7 Establish effective recordkeeping to document the HACCP system. This
would include records of hazards and their control methods, the monitoring of
safety requirements and action taken to correct potential problems.
http://www.cfsan.fda.gov/~lrd/bghaccp.html

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©Johns Hopkins University 2021

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