Transcript The Issue - Food Safety Information

GMO* and Food Safety
Dr. Ted Labuza
Department of Food Science and Nutrition
Univ. Of Minnesota
St Paul 55108
[email protected]
http://fscn.che.umn.edu/Ted_Labuza/tpl.html
* Frankenfoods ???
Safety issues over “GMO”
• Classic toxicity testing
• Substantial equivalence
• Pre-cautionary principal
vs risk benefit
• Identity preservation
• labeling
Poisonous or Deleterious
Substances
•
•
•
•
general toxicity
carcinogens
mutagens
teratogens
FDA Regulation of GMO’s
Food Drug and Cosmetic Act
• 402(a)(1) - a food is adulterated if it
contains any poisonous or
deleterious substance which may
render the food injurious to health
Food Drug and Cosmetic Act
• 402(a)(1) - a food is adulterated if it
contains any poisonous or
deleterious substance which may
render the food injurious to health
– Microbial example : pathogens such as
E. coli O157:H7
Food Drug and Cosmetic Act
• 402(a)(1) - a food is adulterated if it
contains any poisonous or
deleterious substance which may
render the food injurious to health
– Chemical examples : lead,
PCBs, dioxin, mercury,
– radio-nucleotides, pesticides
Food Drug and Cosmetic Act
• 402(a)(1) - a food is adulterated if it
contains any poisonous or
deleterious substance which may
render the food injurious to health
– Relates to unapproved substances
added by man intentionally or nonintentionally
Food Drug and Cosmetic Act
• 402(a)(1) - however if not added*,
the food is not adulterated if the
quantity would not ordinarily
render injurious to health
example - solanine in potatoes
– New level of consumption
– More susceptible population
* meaning naturally present
So could apply to a GMO
Questions
What level of toxicant is tolerable,
if any?
What level of toxicant is
detectable ?
Food Additives Amendment 1958
• 402(a)(2) A food is adulterated if it contains any
added poisonous or deleterious substance
except one that is either:
•
•
•
•
Food Additive (Sec 409)
Generally Recognized As Safe 201(s)
Color Additive (Sec 706)
Pesticide (Sec 408) - clarified as not an additive
• Note that “added” means intentional addition so
would apply to GMO unless exempt as additive or
GRAS
Additive Definition 201(s)
• “ any substance, the intended use
of which may reasonably be
expected to result directly or
indirectly in its becoming a
component or otherwise affecting
the characteristics of any food.”
Additive testing history
•
•
•
•
•
•
Based on traditional toxicity testing
FDA Red Book - 1982 1st edition
LD50 acute toxicity
Sub-acute toxicity
Life time chronic feeding trials
Safety based on 100th of the level of
NOAEL
• Also applied to GRAS substances
Decision process
• Rodricks Food Tech. March 1996 pg 114
• EDI (estimated daily intake) < NRI
(negligible risk intake)
• Assessment
– Natural components
– Unintentional contaminants
– Intentionally added constituents- ADI
• Added 10x10 fold factor to estimate NRI
• GRAS related
Test design constraints for GMO food
• Generally max level of % 5 dry solids in
test animal diet per day
• Equivalent to dose of ~2500 mg/Kg /day
in 50 g diet for 1 Kg animal
• If no effect and use 100x factor then
ADI = 25mg/Kg/day so in 70 Kg human
~1.8 g/day so if GMO with 95%
moisture ~ 1 ounce serving
Sec 409 (c)(3)
Delaney Clause
No regulation shall issue if a fair evaluation before
the Secretary (FDA)
(a) fails to establish that the proposed use shall be
safe provided that no additive shall be deemed
safe it it is found to induce cancer when ingested
by man or animal or if it is found after tests which
are appropriate for their evaluation of the safety
of food additives to induce cancer in man or
animals
Delaney Clause
exclusions
• GRAS substances prior to 1958
• Pesticides - FQP Act
• Dietary supplements (note under NLEA
FDA needs to prove unsafe)
GRAS
• Sec 201 (s)
• Except food additive does not mean such
substance that is generally recognized as safe
(GRAS) among experts qualified by scientific
training and experience to evaluate the safety,
through adequately shown scientific procedures
or in the case of a substance used in food prior to
Jan.1 1958 through either scientific procedures or
common use in food to be safe under the
conditions of its intended use.
Natural Carcinogens
• Mushroom Example AgaratineDNA breaker at 1.2 mg/70 Kg
person
• present in mushrooms
• Calculated safe dose < 4 g
mushroom per day or 1 meal
every 100 days
• Foods are GRAS so exempt
Fmali Herb Inc. v Heckler
• 715 F 2d 1385, 1982 (DC ND CA 9/15/83)
• Block list on renshan-fenwang-jiang from Korea
• Basis not GRAS since not consumed in US prior
to 1958
• Fmali sues to lift ban
• Court agrees that GRAS means anywhere in
world not just US thus if used can bring in
• 53 FR 16544 5/10/88 - substantial use as an
ingredient for food by a significant number of
consumers
GRAS Review 21 CFR 170(f)
• (1) modified substances of natural
biologic origin consumed prior to
1958 but modified afterwards
• (2) significant alteration of prior 1958
natural substances by breeding and
in which the nutritive value or
toxicity changes
Classical Breeding History
• UM, NDSU and USDA potato
research lab development of
improved chipping variety of potato
(Lenape) (Zitnak and Johnston Am Potato Jr
47:256-60)
• Submitted to FDA for approval but
found increased solanine level so
withdrew from introduction
Classical Breeding History
• Discussion at Hort. Science meeting
• published in 1975 Spiher A.T. The
Growing of GRAS Hort Sci. 10:241-42
1975
– Approval based on nutrient level and
toxicological levels
The Issues
• What category of food ingredients do
GMO based varieties it into ?
• What safety criteria are needed in testing,
ie what are the protocols ?
• What does substantial equivalence mean?
• What does “precautionary principal
mean?
1987 National Academy of Sciences
• Introduction of recombinant DNAengineered organisms into the
environment: Key issues
– No evidence of unique hazards
– Risks similar to introduction of
unmodified organisms or those
modified by other methods
The FDA Policy
• 57 FR 22983-23005 May 29, 1992 The safety of
foods derived from new plant varieties
• (Note never finalized -guidance to industry)
– Basic premise is that plant breeding produces safe
foods vs chemicals which may be toxic
– Genetic transferred material may be subject to food
additive or GRAS process
– (DNA itself not a concern IFBC 1990
– Miragila et al 1990 safety assessment of genetically
modified food products Microchem J 59;154-9)
The FDA Policy
• 57 FR 22983-23005 May 29, 1992 The safety of
foods derived from new plant varieties
– Toxicant level suggested ^ by 10% and Nutrient level
suggested decrease of 10%
– Is there a potential allergen ?
– Kessler et. al. The safety of foods developed by
biotechnology Science 256:1747 1992
– Current working policy - 45 products have been
evaluated
– 12 corn, 7 canola, 6 tomato, 5 cotton, 4 potato
– see IFT Expert Report on Biotechnology
http://courses.che.umn.edu/01fscn11021s/general_food_safety/
gmo/gmo.html
Basis of policy
• 402 (a)(1) of FFDC
– see Ronk et al Hort Sci 25;1482-84 1990
• Animal feeding studies problematic
• Animal tests not sensitive as cannot
supplement at high enough level
• Need multidisciplinary assessment process
based on
–
–
–
–
genomic traits
Agronomic and quality analysis
Allergenicity potential
Analysis of toxicants and nutrients
Maryanski, J. FDA’s policy for Foods Developed from
Biotechnology in Genetically Modified Foods: Safety Issues
Engle et al Eds. ACS Symposium Series # 605 1995 pgs 12-22
Basis of policy
• 402 (a)(2) of FFDC
– will need approval as food additive if
introduced protein is different than
normal otherwise GRAS
– Special attention should be given to
potential allergens - see April 1994 FDA
conference on “Scientific issues related to
potential allergenicity in Transgenic Food
Crops FDA Docket # 94N-0053 also in 59 FR
15415 April 1, 1994
OSTP 1994
• Coordinated Framework for US
Biotechnology Policy
– 51 FR 23302 June 26, 1986
• Exercise of Federal oversight
– 57 FR 6753 Feb 24 1992
– Use risk based scientific approach
rather than process used (ie don’t focus
on biotech process rather use the
standard safety evaluation process)
The Genetic Raw Potato
• Ewan and Pusztai Lancet 354:1353-4
Oct. 16, 1999
• Effect of diets containing genetically
modified potatoes expressing
Galanthus nivalis lectin on the rat
small intestine (insect resistance)
• crypt hyperpalsia suggested
expression of other genes
Early Genetic Engineering of GRAS
Ingredients in Foods
• The first round: chymosin
– recombinant technology
– Inserted gene for calf rennet into E. coli
– >80% of world cheese making
Early Genetic Engineering of GRAS
Ingredients in Foods
• The first round: chymosin
– Deemed to be GRAS
– 57 FR 10932-6 23/3/90 E coli
– 57 FR 6476-9:1992 yeast
– 58 FR 27197-203: 1993 mold
• See Flamm E.L. Bio/Technology 9:340-351 ; 1991
–
–
–
–
Same protein structure
Most impurities removed
Organism destroyed in processing
Anti-biotic resistant marker destroyed
Early Genetic Engineering of GRAS
Ingredients in Foods
• High-fructose corn syrup
– recombinant enzymes
– Bound on reactor bead surface so does not go
into food - processing aid
– Converts glucose to fructose
The first controversy - Monsanto
Milk - Recombinant BST or rBGH
Neither GRAS nor Food Additive rather
It is an approved New Animal Drug
Flavor-Savr Tomato
• Calgene asks for food additive status
for enzyme FDA Docket # 90A-0416, 91A-0330
• FDA findings
– enzyme introduced well documented @ <0.16 ppm and
digested 59 FR 26700-711 May 23, 1994
– Marker gene easily digested -FDA suggests that should
use kanamycin marker in all GMO
– Nutrient level the same
– No change in toxic substances- tomatine alkaloid
– No need for special labeling
•
•
Redenbaugh et al Regulatory Issues for the commercialization of
tomatoes with an anti-sense polygalacturonase gene
In-Vitro Cell Devel Biol 29P:17-26 1993
59 FR 26700-711 may 23, 1994
FDA Approvals
•
•
•
•
1994 - squash resistant to diseases
1995 potato insect resistant
1996 Soybean - herbicide resistance
1997 corn - corn borer resistance
WHO-FAO
• 1993 - marker genes not a safety
issue (< 1/250,000 of DNA consumed)
Report 93.6
• 2000 - reconfirms prior statement
“safety aspects of genetically
modified food of plant origin”
Nature Biotechnology Volume 18 Number 11 p 1119; 2000
First, food safety and labeling-the editorial says let's
state once and for all that safety and labeling standards
for foods, food ingredients, and feeds should be applied
regardless of the techniques used in their production
and manufacture. There is widespread Expert
consensus about this (in fact, genetic engineering may
be safer/more precise than conventional breeding), so
why is it even discussed anymore?
Foods should continue to be assessed on the basis of
substantial equivalence, with labeling required only for
(GM) foods that differ significantly in composition or
nutritional value from their conventional counterparts.
Substantial Equivalence Principles
• Term is not in any FDA document
• Reduction by 10% in key nutrients
• Increase by 10% in natural nonadded background toxicants
• New proteins well characterized and
appear in other foods
• Source of gene well characterized
• Need for feeding trials questionable
• Concern for allergenicity - from typical
allergenic food or properties flag as allergen
The Legal Dilemma
• All plants approved have been patented
• Patents are
– New
– Novel
– Non-obvious
– ie Substantially different
OECD 2000
• UN Organization for Economic Cooperation
– Safety of new and novel foods
– Safety based on substantial equivalence
EPA
• FIFRA
– 7 USC 136(a) -136®
– Regulates pesticides
• FQPA 1996
– Pesticide is not a food additive
– Stricter evaluation process especially
with respect to children exposure
EPA principles
• GMO’s are flagged if they are introduced as
a pesticide
• Must submit for approval
• Under FPA pesticide compounds which
include new GMO plant varieties are
excluded from Delaney Clause ie they are
not considered as additives
• Use of precautionary principle
EPA Precautionary Principles
• Mission to protect human health and
safeguard environment within
“adequate margin of safety”
• Question of available data vs need to
extrapolate
• Nature of the risk ie if there is a
carcinogen risk in introduction use
of precautionary assumptions ie
projection of risk on the safe side
USD - APHIS
• Fed Plant Pest Act 7 USC 150 regulates introduction of “plant
pests” that cause injury, death or
damage to any plant 7 CFR 340
GMO: the new potential threat
• Crossing transgenic species
• Brazil nut with soybeans for
methionine
• Fish antifreeze protein in ice cream
Allergenicity flags
Concern for transgenic introduction of allergenic
protein
1. 10 to 70 KDa
2. Resistant to digestion
3. Stable to heat processing
4. Similar to amino acid homology in binding sites
Social Concepts of Risk
Dr. Peter Sandman
• Risk = Hazard + Outrage
Some Definitions
• Hazard = magnitude x probability
– magnitude-how bad it is when something
happens
– probability-how often it is going to happen
• When outrage is zero then
– Risk = Hazard
Hazard is the expected
annual mortality and
morbidity,
and risk assessment
measures this.
Hazard: Scientific Evidence
1. A laboratory study by Cornell
University entomologists indicated
that Bt-corn pollen can kill 44% of
Monarch butterflies
2. British scientist reports that GM
potatoes stunt rats’ growth and
damage their immune system
Outrage is everything about
a risk that is relevant,
EXCEPT how likely it is to
hurt you.
Outrage usually involves
people’s concerns and
fears about a risk rather
than scientific evidence
The Social Concepts of risk
• Risk = Hazard + Outrage
– Fear of the unknown (playing God)
– Voluntary vs in-voluntary
– Dreaded vs non-dreaded (cancer)
• The degree of outrage does not necessarily
correlate to the degree of hazard r2 < 4%
According to Dr. Sandman:
For GM Foods:
RISK = HAZARD + OUTRAGE
The Social Concepts of risk
• Risk = Hazard + Outrage for GMO issue
– Who gets the risk ?
– Trust us
– They are just dumb so if we educate them
they will accept the technology
European Experience
• UK Ministry of Agr said “trust us” on
BSE
• Consumer outrage as result of BSE
incident ~ 80 dead
• 1999 Belgium’s Dioxin contamination
• EU concern over lack of data so
invoke precaution “if don’t know
enough, don’t approve
Risk Perception
Knowledge does not
necessarily lessen
consumer concerns.
Outrage Outcome
• Public pays more attention to outrage
• Activists and media in outrage
business
• Outraged citizens don’t listen to hazard
data
• Outrage is a legitimate process
• When hazard is low - help reduce the
outrage - Don’t make risk comparisons
• Don’t say “they are dumb - all we
• need to do is educate them”
Identity Preservation Outrage
• The Adventis Bt Corn scenario
The Transport Industry
•
•
•
•
•
•
•
Farm truck
Silo
Train car
Barge
Boat
Train car
truck
GMO analytical Needs
• Problems in evaluating %GMO
–On farm or at commercial silo
–Mixing in transport
–Cost of test
–Time to do
–Sample size and reliability
Allergen analysis failure
Problems
extraction
denaturation +/-
need for specific ELISA
not available for most allergens
except peanuts and egg (Neogen)
Starlink Corn
Starlink corn with Cry9C based Bt toxin protein
63FR28258 Bacillus Thuringiensis Subspecies tolworthi Cry9C
Protein and the Genetic Material Necessary for its Production in
Corn;
Exemption from the Requirement of a Tolerance May 22, 1998
EPA allergenicity evaluation
http://www.environmentaldefense.org/pubs/Filings/cry9c.html
• 1. Homology - EPA says no known homology of the 8 amino
acid sequence - but not all known
• 2. Cry9c is resistant to digestion
• 3. Cry9c is stable to thermal processing
• 4. MW (68 kD) is in upper range for allergens
• Thus EPA warned in approval that may be linked to allergens
• Other EPA arguments to allow approval
– Abundance of protein low but patent argues high toxicity
– Low environmental exposure but what about corn dust
Elisa Test Developed
http://www.agdia.com/cgi_bin/catalog.cgi/05600
Starlink Corn problem
• Starlink corn produced by Adventis Corp (Research
Triangle NC ) with Cry9c Bt toxin protein
• Approval given by EPA in 1998 but restricted to animal
feed as noted by potential for allergenic response in
humans based on four criteria
• September 2000 Consumer group (FOE) analyzes taco
shells and finds Cry9c Bt protein. Sept 11, 2000 calls
on EPA to remove
• Taco Bell begins recall of tacos from supermarkets,
as does Safeway product made by Kraft
EPA announcement 10/10/00
Adventis CropScience (NC) is financially
responsible for the screw-up and must pay for it.
Not the farmers fault.
Seeds of Dissent
• The next step : Wednesday,
October 11, 2000 4:48 PM EST
•
WASHINGTON (Reuters) - A biotech corn variety found last month in Taco Bell taco shells and
intended only for use as a livestock feed has been detected in a second human food product, a
consumer advocacy group said on Wednesday.
• Genetically Engineered Food Alert, a coalition of
health, consumer and environmental groups, said it
would announce the product at a news conference on
Thursday.
•
•
•
•
``It'll be a product that people have heard about,'' said Matt Rand, biotechnology specialist for
the National Environmental Trust and co-coordinator of the GE Food Alert campaign.
The group's announcement last month that Taco Bell taco shells sold in grocery stores
contained the Starlink corn variety prompted manufacturer Kraft Foods, a unit of Philip Morris
Cos. Inc. (MO.N), to announce a voluntary recall.
Starlink corn, which is made by Aventis SA (AVEP.PA), has been approved for animal feed but
not for use in human food because of concerns about the potential for allergic reactions.
The U.S. Agriculture Department has said it would buy all of the estimated 45 million bushels
of Starlink corn produced this year to get it off the market. Aventis will reimburse the
department for the expected $90 to $100 million cost of that action.
Starlink Corn problem
• Kellogg’s shuts down corn flakes cereal
plant ( 10/18/2000) as precaution against
potential for allergenic response
• 10/19/00 Adventis says problem is
farmers co-mingled corn into human
food destined corn. Of 260 grain
elevators, about 106 sent out to food
processors which is 12% of Starlink
corn or 9 million bushels
Problem on the farm NY Times 10/17/00
Fred Rosenberger, who grew 40 acres of StarLink corn in Rineyville,
Ky.,this year, was quoted as saying, "We never found out until two weeks
ago,"adding that because he stored the corn before realizing that it should
be segregated, some 8,000 bushels of StarLink corn were mixed in with
about 42,000 bushels of other varieties. Mr. Rosenberger said that some
neighbors,whom he declined to name, had unwittingly shipped it to local
elevators.
Duane Adams, who farms 1,500 acres in Cosmos, Minn., and is vice
president of the Minnesota Corn Growers Association, was cited as saying
that none of the papers that came with StarLink seed he purchased from
Garst last spring carried a warning about the crop's limited use or the
notice that it should be planted at least 660 feet from any other corn.
"I'm sick of it," Mr. Smith said, vowing to never plant another
Aventis product.
Millers and Grocers Reuters 10/10/00
Kroger and Albertsons remove cereal and tacos
Mission Foods recalls all Tacos (largest US
maker)
Azteca Milling will take back all yellow 2 corn
flour
ConAgra stops operations at Kansas corn flour
mill - will not disclose customers
Nov 3 FDA announces over 300 products
with potential risk
The Issue
Green Party (NZ) health spokeswoman Sue
Kedgley was cited as saying on Monday (Oct 30)
that Starlink corn was feared to cause allergic
reactions and digestion problems in some
humans, adding, "Unless the government sets
up an immediate program to randomly monitor
genetically engineered ingredients in our food
supply, it cannot guarantee consumers that their
food is safe."
Is this a realistic problem ?
• Ricki Hall Ark. Children’s Hospital “ Right now
sensitivity to the protein is an unknown…”
• FDA/USDA/EPA says little if any risk
•
Les Crawford Georgetown Univ. “It’s not the human
health risk that is concerning. Its that it got there in the
first place. “
• Cargill Chair W. Staley says although found in some
silos that problem is under control. Will institute new
tests. He notes that problem was irresponsible
procedures by a few in the chain. “There is a
process of protocols to be followed, Unfortunately
people didn’t handle things correctly.”
Steve Taylor Univ. Nebraska
• Statement to EPA
– Would need repeated long time exposure to
Starlink to develop allergy to it
– Cry9C accounts for 0.013% of corn grain
while most allergens at 1 to 40% in food
– “this clearly would not produce proteins
levels of any health concern”
websites
• Northernlight 360 hits in 167 sites
• Friends of earth
http://www.foe.org/act/getacobellpr.html
• Environmental Defense Fund
http://www.environmentaldefense.org/pubs/Filing
s/cry9c.html
• The Campaign
http://www.thecampaign.org/newsupdates/sept00
g.htm
• Lycos http://ens.lycos.com/ens/sep2000/2000L09-18-04.html
Bottom Line
• Many reports since 1990 say there is
no problem with GMO
• Reports include companies and
researchers who might gain from
process so raise the”risk” flag
• But Starlink a different story
• Iowa Governor says will make Adventis
buy back all corn from farmers
• Feb 2001 Farmers say Adventis not
paying up
Clinton Action
• May 3, 2000 Clinton proposes to
finalize 1992 policy
– Require pre-market 75 day notification
process to FDA
The New Next to Final Step
• 66 FR 4706 Jan 18, 2001
• http://courses.che.umn.edu/01fscn11021s/
general_food_safety/gmo/gmo.html
• Good history of regulation of GMOs
• Proposed
– 120 day premarketing notice to FDA
Proposed 21 CFR 192
PBN Premarket Biotechnology Notice
•
•
•
•
•
•
•
Identity
Function
Level
Dietary exposure
Allergenicity
History of use of food in diet
FDA response within 120 days
The Final Step
Labeling - Informed Consent
• Required warnings
– Saccharin
– Aspartame
– Sulfite
– Alcohol
– Meat handling
– irradiation
Labeling - Informed Consent
basis the consumer’s right to know so they
can protect themselves from harm
• Voluntary serious warnings
– allergens
Labeling - Informed Consent
basis the consumer’s right to know so they
can have a freedom of choice
• Voluntary warnings
– Non-GMO
FDA Labeling Guidance Document
• 66 FR 4839 (Jan 18, 2001)
• Guidance Document
– http://vm.cfsan.fda.gov/~dms/biolabgu.html
– Labeling is voluntary
– Food labeling must be truthful ie no GMO need
proof
– If GMO significantly different, common and usual
name should state so
– If allergen present must state so
– Example GMO statements
European Approach
• EC - PP is a political tool to be
invoked when political interests
judge the scientific evidence of
safety to be insufficient ,
inconclusive or uncertain
• Use PP when need absolute proof of
food safety needed
• Recently 2001 approved GMO for
plants but will require labeling
Communication on GMO
• Old style
– Science alone provides objective truths
- ie the proverbial “white paper”
– Science experts are only possible
source of risk evaluation
– Consuming public will listen to “truths”
- but they don’t
Communication on GMO
• New Paradigm
– Right of public to provide input on
public policy decisions
– Free flow of information (but don’t cry
fire in the wrong place”
– Be honest, frank and open
– Issue burnout
URL’s Used in This Slide Show
Presentation.
•
•
•
•
•
•
•
•
www.soybeans.com/newscfm?docuementid=96
www.fmi.org/industry/biotech/
www.aphis.usda.gov/biotechnology/faqs.html
www.ifst.org/hottop10.htm
www.fmi.org/media/bg/biotech.html
www.fda.gov/bbs/topics/consumer/geneg.html
www.extension.iastate.edu/feci/argmo/
www.204202.137.114/onair/worldnewstonight/health/wmt
981109.genfood.html
• http://courses.che.umn.edu/01fscn11021s/general_food_
safety/gmo/gmo.html
Other pertinent material
• IFT Expert Panel Report on
Biotechnology and Foods
– http:// www.ift.org
“There’s a great day dawning if
only we can get through the night