Food Safety: Transgenics and Pesticides

1
Food Safety Transgenics and Pesticides

• Michael Hansen, Ph.D.
• Senior Scientist
• Consumers Union, US
• Conselho Regional de Medicina do Estado de São
  Paulo
• São Paulo, Brazil
• April 26, 2010

2
Outline

• A. US FDA Policy on Genetically Engineered
  plants
• B. Bt crops--potential allergenicity and
  immunogenicity concerns
• C. Unexpected Effects
• D. Do GE crops reduce pesticide use?
• E. Toxicity of glyphosate
• F. Conclusion

3
FDA Policy on Genetically Engineered Plants

• Introduced at press conference at an industry
  gathering on May 27, 1992 by then Vice-President
  Dan Quayle as a deregulatory initiative
• Based on notion that the new techniques e.g.
  genetic engineering are extensions at the
  molecular level of traditional methods and will
  be used to achieve the same goals as traditional
  plant breeding (57 FR 22991, May 29, 1992)
• No requirement for human safety testing, only
  voluntary safety consultations to date, some
  80 voluntary safety consultations have been held

4
Key phrases in US Food and Drug Administration
safety consultation letters

• Letter for MON 810 (Bt corn), dated Sept. 26,
  1996
• Monsanto submitted a summary assessment of corn
  containing transformation event MON 810 on June
  6, 1996
• Based on the safety and nutritional assessment
  you have conducted, it is our understanding that
  Monsanto has concluded that corn products derived
  from this new variety are not materially
  different in composition, safety, and other
  relevant parameters from corn currently on the
  market, and that the genetically modified corn
  does not raise issues that would require
  premarket review or approval by FDA.
  www.cfsan.fda.gov/acrobat2/bnfL034.pdf
• These two sentences found in all 80 safety
  consultation letters
• FDA does not require premarket safety assessment
  and does not state its own opinion about the
  safety of the GE crop

5
Bt crops

• Engineered with endotoxins produced by the soil
  bacterium Bacillus thuringiensis
• Endotoxins are called Cry proteins and there are
  many of them
• Bt crops on market include corn, potato, cotton,
  poplars many are in testing phase, including Bt
  rice, Bt brinjal, Bt soy
• Concern over allergenicity and immunological
  impacts of Cry proteins on the gut

6
Joint FAO/WHO Expert Consultation on
Allergenicity of Foods Derived from
Biotechnology, January, 2001

• http//www.fao.org/es/ESN/food/risk_biotech_allerg
  en_es.stm
• Conclusions
• The Consultation emphasized that all foods
  derived from biotechnology must be assessed for
  allergenic potential

7
Joint FAO/WHO Expert Consultation on
Allergenicity of Foods Derived from
Biotechnology, January, 2001

• 7. The Consultation was of the opinion that an
  evaluation of proteins for sequence homology with
  sufficient sensitivity and specificity to detect
  potential cross-reactivity is an important part
  of the process for the assessment of the
  allergenicity of the expressed protein.

8
Joint FAO/WHO Expert Consultation on
Allergenicity of Foods Derived from
Biotechnology, January, 2001

• 6.1. Sequence Homology as Derived from Allergen
  Databases
• The commonly used protein databases (PIR,
  SwissProt and TrEMBL) contain the amino acid
  sequence of most allergens for which this
  information is known. However, these databases
  are currently not fully up-to-date. A
  specialized allergen database is under
  construction.
• Cross-reactivity between the expressed protein
  and a known allergen (as can be found in the
  protein databases) has to be considered where
  there is 1) more than 35 identity in the amino
  acid sequence of the expressed protein (i.e.
  without the leader sequence, if any), using a
  window of 80 amino acids and a suitable gap
  penalty (using Clustal-type alignment programs or
  equivalent alignment programs) or 2) identity
  of 6 contiguous amino acids.
• If any of the identity scores equals or exceeds
  35, this is considered to indicate significant
  homology within the context of this assessment
  approach. The use of amino acid sequence
  homologies to identify prospective cross-reacting
  allergens in genetically-modified foods has been
  discussed in more detail elsewhere (Gendel,
  1998a, Gendel, 1998b).

9
Joint FAO/WHO Expert Consultation on
Allergenicity of Foods Derived from
Biotechnology, January, 2001

• Recommendations
• 1. The Consultation recommends that the FAO/WHO
  2001 decision tree be used for determining
  allergenicity of foods derived from biotechnology

10
Joint FAO/WHO Expert Consultation on
Allergenicity of Foods Derived from
Biotechnology, January, 2001

• Recommendations
• 1. The Consultation recommends that the FAO/WHO
  2001 decision tree be used for determining
  allergenicity of foods derived from biotechnology

11
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12
Kleter, G.A. and A.C.M Peijnenburg. 2002.
Screening of transgenic proteins expressed in
transgenic food crops for the presence of short
amino acid sequences identical to potential,
IgE-binding linear epitopes of allergens. BMC
Structural Biology, 2 8.

• www.biomedcentral.com/1472-6807/2/8
• Compare transgenic protein from GE/GM crop with
  known allergen, looking for identical stretches
  of at least 6 amino acids
• Screen positives further with
• Epitope database
• Antigenicity prediction algorithm

13
Kleter, G.A. and A.C.M Peijnenburg. 2002.
Screening of transgenic proteins expressed in
transgenic food crops for the presence of short
amino acid sequences identical to potential,
IgE-binding linear epitopes of allergens. BMC
Structural Biology, 2 8.
14
Kleter, G.A. and A.C.M Peijnenburg. 2002.
Screening of transgenic proteins expressed in
transgenic food crops for the presence of short
amino acid sequences identical to potential,
IgE-binding linear epitopes of allergens. BMC
Structural Biology, 2 8.
15
Kleter, G.A. and A.C.M Peijnenburg. 2002.
Screening of transgenic proteins expressed in
transgenic food crops for the presence of short
amino acid sequences identical to potential,
IgE-binding linear epitopes of allergens. BMC
Structural Biology, 2 8.
16
Kleter, G.A. and A.A.C.M Peijnenburg. 2002.
Screening of transgenic proteins expressed in
transgenic food crops for the presence of short
amino acid sequences identical to potential,
IgE-binding linear epitopes of allergens. BMC
Structural Biology, 2 8.

• Only a limited number of identical stretches
  shared by transgenic proteins (papaya ringspot
  virus coat protein, acetolactate synthase GH50,
  and glyphosate oxioreductase) and allergenic
  proteins could be identified as (part of)
  potential linear epitopes. . . The positive
  outcomes of this approach warrant further
  clinical testing for potential allergenicity.

17
Gendel, S.M. 1998b. The use of amino acid
sequence alignments to assess potential
allergenicity of proteins used in genetically
modified foods. Advances in Food and Nutrition
Research, 42 44-61.

• although it is clear that some amino acid
  residues are critical for specific binding, some
  conservative substitutions may not affect
  allergenicity. Therefore, it may be prudent to
  treat sequence matches with a high degree of
  identity that occur within regions of similarity
  as significant even if the identity does not
  extend for eight or more amino acids. For
  example, the similarity between Cry1A(b) and
  vitellogenin might be sufficient to warrant
  additional evaluation (Gendel, 1998b 60).

18
Fares, NH AK El-Sayed. 1998. Fine structural
changes in the ileum of mice fed on
delta-endotoxin-treated potatoes and transgenic
potatoes. Natural Toxins 6 219-233.

• Bt-potatoes and Bt-toxin (Cry 1) caused
  disruption, multinucleation, swelling, increased
  degradation of ileal (gut) surface cells in rats.
  Effect worse with Bt-toxin
• These effects demonstrate that Bt-toxin survives
  digestion in functionally and immunologically
  active form

19
Fares, NH AK El-Sayed. 1998. Fine structural
changes in the ileum of mice fed on
delta-endotoxin-treated potatoes and transgenic
potatoes. Natural Toxins 6 219-233.

• These changes may suggest that
  delta-endotoxin-treated potatoes resulted in the
  development of hyperplastic cells in the mice
  ileum. Although mild changes are reported in the
  structural configuration of the ileum of mice fed
  on transgenic potatoes, nevertheless, thorough
  tests of these new types of genetically
  engineered crops must be made to avoid the risks
  before marketing. (Fares and Sayed, 1998 219)

20
Vazquez-Padron, R.I., Moreno-Fierros, L.,
Neri-Bazan, L., de la Riva, G.A. and R.
Lopez-Revilla. 1999b. Bacillus thuringiensis
Cry1Ac protoxin is a potent systemic and mucosal
adjuvant. Scandinavian Journal of Immunology 49
578-584

• We conclude that Cry1Ac is a mucosal and
  systemic adjuvant as potent as CT cholera toxin
  which enhances mostly serum and intestinal IgG
  antibody responses (Vazquez-Padron et al.,
  1999b pg. 578).
• Cry1Ac is potent stimulator of immune system
• Cry1Ac survives digestion

21
Vazquez-Padron, R.I., et al. 2000b. Cry1Ac
protoxin from Bacillus thuringiensis sp. kurstaki
HD73 binds to surface proteins in the mouse small
intestine. Biochemical and Biophysical Research
Communications 271, pp. 54-58

• we demonstrated that Cry1Ac protoxin (pCry1Ac)
  binds to the mucosal surface of the mouse small
  intestine . . . six pCry1Ac-binding polypeptides
  present in brush border membrane vesicles
  isolated from the small intestine. Moreover,
  this protein induced in situ temporal changes in
  the electrophysiological properties of the mouse
  jejunum. The data obtained indicate a possible
  interaction in vivo of Cry proteins with the
  animal bowel which could induce changes in the
  physiological status of the intestine
  (Vazquez-Padron et al., 2000b 54).

22
Vazquez-Padron, R.I., et al. 2000b. Cry1Ac
protoxin from Bacillus thuringiensis sp. kurstaki
HD73 binds to surface proteins in the mouse small
intestine. Biochemical and Biophysical Research
Communications 271, pp. 54-58

• We think that previous to commercialization of
  food elaborated with self-insecticide transgenic
  plants it is necessary to perform toxicological
  tests to demonstrate the safety of Cry1A proteins
  for the mucosal tissue and for the immunological
  system of animals (Vazquez-Padron et al., 2000b
  58).

23
Bernstein, et al. 1999. Immune responses in
farm workers after exposure to Bacillus
thuringiensis pesticides. Environmental Health
Perspectives, 107(7) 575-582

• Scientists did study on farm workers in onion
  fields in Ohio, US that were exposed to Bt sprays
• reactivity IgE antibodies to the Btk
  pro-delta-endotoxin was encountered in 2 of 123
  workers sensitized by the respiratory route . . .
  future clinical assessment of this possibility
  is now feasible because of the availability of
  reliable Bt skin and serologic reagents developed
  during the course of this investigation
  (Bernstein et al., 1999 pg. 581).

24
Bernstein, et al. 2003. Clinical and laboratory
investigation of allergy to genetically modified
foods. Environmental Health Perspectives,
111(8) 1114-1121.

• Workers in agricultural and food preparation
  facilities have potential inhalation exposure to
  plant dusts and flours. In 1999, researchers
  found that migrant health workers can become
  sensitized to certain Bt spore extracts after
  exposure to Bt spraying. Thus, the potential for
  occupational and consumer risks needs to be
  assessed.

25
Impact of Bt cotton on farmers health (in
Barwani and Dhar District of Madhya Pradesh) Dr.
Ashish Gupta et al. Investigation Report Oct.
Dec. 2005www.gmwatch.org/print-archive2.asp?arcid
6265

• Surveyed 5 villages, talked to people with
  symptoms and exposure to Bt cotton N 23
• All had skin symptoms, primarily itching (23),
  redness (19), or eruptions (20). The symptoms
  tended to occur on face (17), hands (15), feet
  (11)
• Almost half (11) had eye symptomsitching,
  redness and/or swelling
• About 40 (9) had upper respiratory tract
  symptoms runny nose and/or excessive sneezing
• Almost 90 had moderate (10) or severe symptoms
  (10)

26
Impact of Bt cotton on farmers health (in
Barwani and Dhar District of Madhya Pradesh Dr.
Ashish Gupta et al. Investigation Report Oct.
Dec. 2005www.gmwatch.org/print-archive2.asp?arcid
6266

• Symptoms overwhelmingly on exposed parts of body
  (face, hand, feet, neck, eyes and respiratory
  tract). Only 1 of 23 had symptoms only on
  covered parts of body (14 exposed body parts
  only, 8 both)
• Almost 80 (18) exposed in cotton field, 4
  exposed at home
• Almost 74 (17) directly involved in picking
  cotton
• People that symptoms increased in severity when
  they continued to work in fields and decreased
  when they stopped work
• Symptoms started within last two years, when Bt
  cotton was introduced

27
Impact of Bt cotton on farmers health (in
Barwani and Dhar District of Madhya Pradesh Dr.
Ashish Gupta et al. Investigation Report Oct.
Dec. 2005www.gmwatch.org/print-archive2.asp?arcid
6266

• Ginning factory
• Owner noted that most of the farmers and
  labourers were having skin related problems due
  to Bt cotton
• Detailed interview with 6 workers in different
  ginning factories found all had itching problems
  on exposed parts of body (hands, legs, face), and
  2 were having eruptions on body
• Workers had been in factory from 2 7 years, but
  symptoms only began last year, with introduction
  of Bt cotton

28
MON 863

• MON 863Monsanto Bt maize for corn rootworm (with
  Cry3Bb1)
• Approved in US and in EU
• Monsanto submission revealed significant effects
  on organs and blood parameters (Séralini et al.
  2007. New analysis of a rat feeding study with a
  genetically modified maize reveals signs of
  hepatorenal toxicity. Arch Environ Contam
  Toxicol, 52 596-602.)
• Increased basophils, lymphocytes and white
  blood cells. Decreased reticulocytes
• Decreased kidney weight
• Increased blood sugar

29
Vendômois, JS, Roullier, F, Cellier, D and GE
Séralini. 2009. A comparison of the effects of
three GM corn varieties on mammalian health.
International Journal of Biological Sciences,
5(7) 706-726.

• Study obtained Monsantos submission to EU for 3
  GE corn varieties (NK 603, MON 810, MON 863) and
  reanalyzed all the data
• Approximately 60 different biochemical
  parameters were classified per organ and measured
  in serum and urine after 5 and 14 weeks of
  feeding.

30
Vendômois, JS, Roullier, F, Cellier, D and GE
Séralini. 2009. A comparison of the effects of
three GM corn varieties on mammalian health.
International Journal of Biological Sciences,
5(7) 706-726.

• Our analysis clearly reveals for the 3 GMOs new
  side effects linked with GM maize consumption,
  which were sex- and often dose-dependent.
  Effects were mostly associated with the kidney
  and liver, the dietary detoxifying organs,
  although different between the 3 GMOs. Other
  effects were also noticed in the heart, adrenal
  glands, spleen and haematopoietic system. We
  conclude that these data highlight signs of
  hepatorenal toxicity, possibly due to the new
  pesticides specific to each GM corn. In
  addition, unintended direct and indirect
  metabolic consequences of the genetic
  modification cannot be excluded.

31
Zolla, L. et al. 2008. Proteomics as a
Complementary Tool for Identifying Unintended
Side Effects Occurring in Transgenic Maize Seeds
As a Result of Genetic Modifications. Journal of
Proteome Research, 7 1850-1861.

• Proteomics is the study of expressed proteins.
  This is good way to detect unintended effects
  associated with GE, particularly the disruptive
  effects due to the random insertion of transgene
• Superior study design GE maize (MON810) and
  near isoline grown side-by-side in growth
  chamber, to control for environmental effects

32
Zolla, L. et al. 2008. Proteomics as a
Complementary Tool for Identifying Unintended
Side Effects Occurring in Transgenic Maize Seeds
As a Result of Genetic Modifications. Journal of
Proteome Research, 7 1850-1861.

• Results 43 proteins resulted up- or
  down-regulated in transgenic seeds with respect
  to their controls (T06 vs WT06), which could be
  specifically related to the insertion of a single
  gene into a maize genome by particle
  bombardment. (pg. 1850). Of these 43 proteins,
  14 were down-regulated, 13 up-regulated, 9 shut
  off and 7 newly expressed.
• Interestingly, a newly expressed spot (SSP 6711)
  corresponding to 50 kDa gamma zein, a well-known
  allergenic protein, has been detected. Moreover,
  as a major concern, a number of seed storage
  proteins (such as globulins and vicilin-like
  embryo storage proteins) exhibited truncated
  forms having molecular masses significantly lower
  than the native ones. (pg. 1855)

33
Finamore, A et al. 2008. Intestinal and
Peripheral Immune Response to MON810 Maize
Ingestion in Weaning and Old Mice. Journal of
Agricultural and Food Chemistry

• Well designed study MON810 and near isoline
  grown simultaneously in neighboring fields in
  Landriano, Italy, to control for environmental
  effects
• This study evaluated the gut and peripheral
  immune response to genetically modified (GM)
  maize in mice in vulnerable conditions. Weaning
  and old mice were fed a diet containing MON810 or
  its parental control maize . . . for 30 and 90
  days. . . As compared to control maize, MON810
  maize induced alterations in the percentage of T
  and B cells and of CD4, CD8, ?dT, and RT
  subpopulations of weaning and old mice fed for 30
  or 90 days, respectively, at the gut and
  peripheral sites. An increase of serum IL-6,
  IL-13, IL-12p70, and MIP-1 cytokines involved in
  allergenic and inflammatory response after
  MON810 feeding was also found. These results
  suggest the importance of the gut and peripheral
  immune response to GM crop ingestion as well as
  the age of the consumer in the GMO safety
  evaluation.

34
Velirimov et al. 2008. Biological effects of
transgenic maize NK603xMON810 fed in long term
reproduction studies in mice.

• Very carefully designed Austrian long-term
  feeding study. The non-GE maize control was a
  near isogenic line. Both control and GE maize
  were grown in adjacent fields in Canada in the
  same year (2005, 2007), to control for
  environmental effects. Large sample sizes were
  used to detect more subtle adverse effects.
• Major result statistically significant adverse
  reproductive effects shown in the reproductive
  assessment by continuous breeding (RACB) study.
  RACB is a feeding study whereby a pair of mice
  are fed GM maize for 140 days, during which time
  the female is bred so that she delivers 4
  litters. RACB puts mice under stress making it
  easier to detect adverse effects.

35
Velirimov et al. 2008. Biological effects of
transgenic maize NK603xMON810 fed in long term
reproduction studies in mice.

• From 24 pairs assigned to the ISO and GM group,
  all females of the ISO group (100) delivered 4
  litters. In the GM group the number of deliveries
  declined with time. In the 4th litter only 20
  deliveries occurred (p0.055). The average number
  of pups born was always lower in the GM group but
  not significant before the 3rd delivery. There
  were significantly fewer pups born in the GM
  group in the 3rd (p 0.011) and 4th (p0.010)
  delivery and weaned in the 4th litter (p0.025).
  Regarding all deliveries per group more pups were
  born in the ISO than in the GM group (1035 versus
  844). Furthermore females of the GM group always
  had smaller litters (n lt 8) as compared to
  females of the ISO group.

36
Benbrook, C. 2004. Genetically engineered crops
and pesticide use in the United States The
first nine years. At http//www.biotech-info.ne
t/Full_version_first_nine.pdf
37
Benbrook, C. 2004. Genetically engineered crops
and pesticide use in the United States The
first nine years. At http//www.biotech-info.ne
t/Full_version_first_nine.pdf
38
Benbrook, C. 2009. Genetically engineered crops
and pesticide use in the United States The
first thirteen years.

• During first 9 years, pesticide use on
  genetically engineered crops was increased by a
  total of 122 million pounds.
• Update on the Benbrooks 2004 paper Bt corn
  and cotton has reduced insecticide use by 56
  million pounds, but herbicide tolerant crops have
  increased pesticide use by 383 million pounds,
  for an overall 327 million pounds increase over
  the 13 years.
• So, for 1996-2004, 122 million pounds more
  pesticide was used on GE compared to non-GE
  crops. For 2005-2008, an additional 205 million
  extra pounds were applied.

39
Wang, S., Just, D.R. and P. Pinstrup-Andersen.
Tarnishing Silver Bullets Bt technology
adoption, bounded rationality and the outbreak of
secondary pest infestations in China. Paper
presented at American Ag. Econ. Assoc. annual
meeting, Long Beach, CA, 22-26 July, 2006

• Household survey of 481 farmers, 20 villages, 5
  provinces Hebei, Shandong, Henan, Anhui, Hubei
• Results for 2004
• Average expenditure on pesticides was same (
  US101/ha) between Bt and non-BT farmers
• Bt farmers spend 46 less on bollworm pesticide,
  but spend 40 more on pesticides for secondary
  pest(s), compared to non-Bt farmers
• Main secondary pest mirids
• GM cotton seeds cost 3 times more than non-Bt
  cotton, so Bt farmers make less money than non-Bt
  farmers
• Results markedly different from data from 1999,
  2000, 2001

40
Wang, S., Just, D.R. and P. Pinstrup-Andersen.
Tarnishing Silver Bullets Bt technology
adoption, bounded rationality and the outbreak of
secondary pest infestations in China. Paper
presented at American Ag. Econ. Assoc. annual
meeting, Long Beach, CA, 22-26 July, 2006
41
Wang, S., Just, D.R. and P. Pinstrup-Andersen.
Tarnishing Silver Bullets Bt technology
adoption, bounded rationality and the outbreak of
secondary pest infestations in China. Paper
presented at American Ag. Econ. Assoc. annual
meeting, Long Beach, CA, 22-26 July, 2006
42
Wang, S., Just, D.R. and P. Pinstrup-Andersen.
Tarnishing Silver Bullets Bt technology
adoption, bounded rationality and the outbreak of
secondary pest infestations in China. Paper
presented at American Ag. Econ. Assoc. annual
meeting, Long Beach, CA, 22-26 July, 2006
43
Do GE crops reduce pesticide use?

• farmers have rotated RR crops, usually soya and
  maize, to the point that the weeds themselves are
  now Roundup resistant, which has resulted in much
  higher applications of Roundup along with a host
  of other chemicals. Nathalie Moll, EuropaBio.
  In GM crops Biotech agricultureTime to take
  GM seriously, Ethical Corporation, February 7,
  2008 At www.ethicalcorp.com/content.asp?ContentI
  D5684

44
Richard, S. et al. 2005. Differential effects
of glyphosate and Roundup on human placental
cells and aromatase. Environmental Health
Perspectives, 113(6) 716-720.

• Exposure of male farmers in Ontario, Canada to
  glyphosate-based herbicides was associated with
  increase in miscarriage and premature birth in
  farm families (Savitz et al. 1997. Male
  pesticide exposure and pregnancy outcome. Am J
  Epidemiology, 146 1025-1036.) this study tried
  to look at possible mechanisms.
• Design incubated human placental JEG3 cells
  with various concentrations of Roundup (up to 2)
  or equivalent concentrations of glyphosate. Cell
  viability was measured after 18, 24, and 48
  hours. Aromatase (which regulates estrogen
  synthesis) levels were measured after 1 hour and
  18 hours.
• Results 2 Roundup and an equivalent
  concentration of glyphosate killed 90 of the
  JEG3 cells after 18 hours incubation. Median
  lethal dose for Roundup (0.7) was approximately
  1.8 times lower than for glyphosate. Viability
  of cells exposed to glyphosate was considerably
  reduced when just 0.1 Roundup was added.

45
Richard, S. et al. 2005. Differential effects
of glyphosate and Roundup on human placental
cells and aromatase. Environmental Health
Perspectives, 113(6) 716-720. Contd

• Results After 1 hour incubation with Roundup,
  aromatase activity increased by 40. After 18
  hours, synthesis was inhibited, with a median
  inhibiting concentration (IC50) of 0.04, perhaps
  reflecting an effect on aromatase gene
  expression. No effect was seen with glyphosate
  alone.
• In sum, study showed that effect of Roundup on
  cell viability increased with time and was
  obtained with concentrations of Roundup 10 times
  lower than those recommended for agricultural
  use. Roundup also disrupted aromatase activity
  at concentrations 100 times lower than those used
  in agriculture.

46
Eriksson, S., Hardell, L et al. 2008. Pesticide
exposure as risk factor for non-Hodgkin lymphoma
including histopathological subgroup analysis.
Int. J. of Cancer, 123 1657-1663.

• Design Population based case-control study.
  910 NHL cases (male and female age 18-74 years,
  living in Sweden, from December 1, 1999, to April
  30, 2002) and 1016 controls.
• Results Exposure to phenoxyacetic acids yielded
  odds ration (OR) 2.04 (95 confidence interval
  CI 1.18-2.51). Exposure to glyphosate gave OR
  of 2.02, 95 CI 1.10-3.71 and with gt10 years
  latency period OR was 2.26, 95 CI 1.16-4.40.
• Previous study involving pooled analysis of 2
  Swedish case-control studies showed OR for
  glyphosate of 3.04 (95 CI 1.08-8.52). (Hardell,
  L., Eriksson, M and M. Nordstrom. 2002.
  Exposure to pesticides as risk factor for
  non-Hodgkins lymphoma and hairy cell leukemia
  pooled analysis of two Swedish case-control
  studies. Leukemia Lympoma, 1043-1049)
• Conclusion our study confirmed an association
  between exposure to phenoxyacetic acids and NHL
  and the association with glyphosate was
  considerably strengthened.

47
Conclusion

• 1. US FDA does not require preapproval safety
  assessments
• 2. The endotoxins in Bt crops raise issues of
  allergenicity and immunogenicity
• 3. Feeding studies have found unexpected adverse
  effects
• 4. Between 1995-2009, GE crops in US have
  increased use of herbicides, particularly
  glyphosate, by 383 million pounds and decreased
  insecticide use by 56 million pounds
• 5. Roundup appears to be an endocrine disruptor
  and has been linked to increased risk of
  Non-Hodgkins lymphoma

48
Codex Alimentarius Principles for the Risk
Analysis of Foods Derived from Modern
Biotechnology (CAC/GL 44 2003)

• 18. Risk managers should take into account the
  uncertainties identified in the risk assessment
  and implement appropriate measures to mange these
  uncertainties
• 19. Risk management measures may include, as
  appropriate, food labelling, conditions for
  market approval and post-market monitoring
• (paras 18, 19 CAG/GL 44-2003)

49
Codex Alimentarius Guideline for Conduct of
Food Safety Assessment of Foods Derived from
Modern Biotechnology (CAC/GL 45 2003)

• Unintended effects due to genetic modification
  may be subdivided into two groups those that
  are predictable and those that are unexpected
  . . . A variety of data and information are
  necessary to assess unintended effects because no
  individual test can detect all possible
  unintended effects or identify, with certainty,
  those relevant to human health. These data and
  information which considered in total, provide
  assurance that the food is unlikely to have an
  adverse effect on human health italics added
  (paras 16 and 17, CAG/GL 45-2003)

50
Codex Alimentarius Guideline for Conduct of
Food Safety Assessment of Foods Derived from
Modern Biotechnology (CAC/GL 45 2003)

• Molecular biological and biochemical techniques
  (that) can also be used to analyse potential
  changes at the level of gene transcription and
  message translation that could lead to unintended
  effects (para 16, CAG/GL 45-2003)

51
Unintended Effects

• Belgian scientists looked at molecular
  characterization of 6 transgenic crops 3 Bt
  maizes herbicide tolerant maize (LibertyLink
  maize) glyphosate tolerant soybeans, and a
  canola engineered for male sterility
• In all but canola, structure of transgenic
  inserts differed between a companys initial
  submission and subsequent studies. Differences
  involved rearranged inserts, partial copies of
  genes inserted, multiple copies of transgenes
  inserted, scrambling of DNA near the border of
  the transgenic inserts, etc., instability and/or
  more likely to result in unintended effects.
• Scientists recommend that further analysis
  should be done to determine the presence of
  chimaeric open reading frames in the border
  integration sequences, e.g. are any unexpected
  proteins being produced?

52
Codex Alimentarius Annex on the Assessment of
Possible Allergencity of the Guideline for the
Conduct of Food Safety Assessment of Foods
Derived from Recombinant-DNA Plants

• 2. At present, there is no definitive test that
  can be relied upon to predict allergic response
  in humans to a newly expressed protein (para 2,
  Annex, CAG/GL 45-2003)