Professional Documents
Culture Documents
THE basic
tenet of all
Toxicology:
“The dose
alone
makes the
poison.”
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Risk Assessment Paradigm
§ Hazard Identification - Determination of adverse effects caused
by high intakes of the chemical (epidemiology, clinical, animal,
short-term and specialized studies)
§ Dose-Response Assessment
§ Selection of critical data set and toxic effect levels
§ Determination of Uncertainty or Safety Factors
§ Derive an Acceptable Daily Intake (ADI)
§ Risk Characterization
§ Estimation of the fraction of the population exceeding ADI
§ Evaluation of the magnitude of potential excess intakes.
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Increasing concerns related to the
potential chemical hazards in food
n More sensitive analytical methods
n Non-balanced discussion
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Food and Chemical Safety Issues
§ We usually test individual food chemicals, not the whole foods
or beverages (except with epidemiology)
§ For whole foods, we must identify biologically active toxic
component(s)
§ Must determine appropriate mechanism of action of specific
chemicals (carcinogens, reproductive toxicants, etc.)
§ Key importance of dose-response relationships
§ Interactions with diet/nutrients, environment & drugs
§ Explore sensitive segments of population (young, pregnant,
aging)
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Human Relevance of Rodent Cancer Bioassays is
Being Questioned
§ Some eminent toxicologists have questioned the human
relevance of tumors seen in lifetime rodent bioassays, and they
believe it’s time to STOP doing chronic rodent bioassays at the
“Maximum Tolerated Dose” (MTD)
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Goal - To bring together and summarize relevant research on
the use and biology of Energy Drinks and to highlight the most
critical research gaps. Sponsored by NIH Office of Dietary
Supplements and several other NIH Institutes. Talks focused
on patterns of use, sensitive subpopulations, safety and
health effects of Energy Drinks and their ingredients.
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Acrylamide Snapshot: Chemistry and Toxicology
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Gener al Scheme of Maillar d Br owning Reaction
Ammonia Melanoidins
Alkyl amines (pigments)
Amine Amino acids
Proteins HEAT
Phospholipids
Amino-Car bonyl
Volatile Compounds
Inter action
(aroma chemicals)
(Amador i Pr oducts)
Aldehydes
Ketones Carbonyls
Car bonyl Sugar s Esters
Furans Oxazoles Amides (Acr ylamide)
Carbohydrates Pyrroles Imidazoles
Lipids Thiophenes Pyridines
Heterocyclic Compounds
Thiazoles Pyrazines
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Food Acrylamide Range (ppb)
Baby food/biscuits ND - 442
Cereals 11 - 1057
Coffee (brewed) 5 - 11
Cookies/crackers 26 - 1540
Dairy drinks ND - 43
Fruits/vegetables (canned) ND - 83
Gravies/seasonings ND - 151
Infant formulas ND
ü 2-year cancer bioassay in rats and mice fed acrylamide in drinking water
(untreated control + 4 treatment doses), with ancillary studies on
metabolism, genotoxicity and toxicokinetics
ü NTP Technical Report No. 575 for Acrylamide was peer-reviewed in April
2011; Panel accepted conclusions that there was “Clear Evidence of
Carcinogenicity” in male & female rats and male & female mice
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“Acrylamide in Foods: A Review of the Science and
Future Considerations”
David R. Lineback, James R. Coughlin and Richard H. Stadler,
Ann. Rev. Food Sci. & Technol. 3: 15-35 (April 2012)
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Acrylamide Battleground under California Prop 65
ü French fries: Attorney General sued and settled case (2008) against
frozen fries/tater tots demanding a 50% reduction in levels; fast-food
restaurant fries have had cancer warnings posted for years
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Acrylamide in Coffee Battles under Prop 65
ü Private “bounty hunter” group (CERT) sued coffee shops
(Starbucks, Peet’s, etc.) in April 2010 for failure to provide cancer
warnings (“brewed coffee” suit); in April 2011, the shops began
posting 10 x 10 inch cancer warning placards covering coffee,
baked goods and other products
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Furan
ü Maillard Browning compound; rat and mouse liver carcinogen (NTP, 1993)
and “possibly carcinogenic to humans” (IARC, 1995); FDA, EFSA and Health
Canada have all provided data analyses and exposure assessments
ü “Margin of Exposure” = 750 - 4,300 below the lowest rodent risk level
(Carthew et al., 2010) & less potent than acrylamide; JECFA (2010) concluded
that dietary exposures to furan “indicate a human health concern for a
carcinogenic compound which may act via a DNA-reactive metabolite”
ü Brewed coffee is about 70% of total furan exposure, the highest dietary
contributor of all foods and beverages; up to 200 ppb in some coffees, but is
reduced significantly during roasting, grinding, storage, brewing and
drinking; levels actually closer to 10 - 35 ppb.
ü But coffee PROTECTS against human liver cancer: “Coffee / Cancer Paradox”
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4-Methylimidazole (4-MEI) under Prop 65
ü Maillard Browning Reaction chemical occurs naturally in added caramel colors
(cola beverages, darker beers) and in many browned foods/beverages (coffee, soy
sauce, others); JECFA set level not to exceed 200-250 ppm Class III and IV)
ü Proposed for carcinogen listing by “AB” (NTP bioassay) in Jan. 2008; listed in
Jan. 2011 after we waged a fierce scientific battle
ü NTP cancer bioassay (2007) showed only increased lung tumors in mice; but it
reduced many other tumors in rats; this made no difference to OEHHA
ü OEHHA adopted safe harbor NSRL = 29 µg/day in Feb. 2012; we believe it should
be much higher
ü Industry coalition sued OEHHA to reverse listing Feb. 2011 but lost case in Nov;
went to appeal Feb. 2012, but appeal abandoned by industry Aug. 2012
ü Center for Environmental Health, 60-Day Notices (Jan/Feb. 2012): Dr. Pepper
Snapple Group, Safeway, Save Mart Supermarkets, Wal-Mart, Coke, Pepsi, Cott,
Trader Joe’s, Walgreen; lawsuits were threatened
Chromium Picolinate
Ginseng αβ-Thujone NOT SUFFICIENT NO
Milk Thistle Extract
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Arsenic and Lead
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Environmental Law Foundation Suit in Alameda
County Superior Court over Lead
ü Major victory for food industry – no need for birth defects warnings
for lead
ü The judge also decided, however, that the defendants did not show
by a preponderance of the evidence that Prop 65 is:
1) Federally preempted or
2) That the regulatory defense of “naturally occurring” is applicable
to their products.
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FDA Chemical Contaminant of Concern in
Food - Inorganic Arsenic
ü FDA’s Total Diet Study (TDS) had been measuring arsenic
in food commodities for over 20 years
ü FDA said It is appropriate to set an action level for iAs because their
sampling data show that inorganic arsenic is the main form of arsenic in
apple juice and because iAs is considered more toxic than organic arsenic
species
ü FDA will continue to screen apple juice samples for total arsenic, prior to
speciating for iAs in samples with total arsenic levels above 10 ppb
ü FDA also concluded that an action level of 10 ppb is adequate to protect the
public health based on its risk assessment.
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Inorganic Arsenic in Rice Data Evaluation
ü ~ 1,300 data samples (200 samples from Sept. 2012)
ü FDA’s main message – “Amount of detectable iAs is too low in the rice and
rice product samples to cause any immediate or short-term adverse health
effects.”
ü Next steps –
ü Exposure and risk assessments for long-term exposure to very low
amounts of iAs (cancer endpoints)
ü Release sometime in 2014 for public comments
ü Will eventually decide if further actions are required (i.e., action levels)
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“Benefit-Risk Evaluation” to Assess the Safety of
Foods Containing Toxicants and Carcinogens
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