(August
2018)
Zdziarski et al published a paper in Food and Nutrition
Sciences on a 26 week feeding study in rats using GM corn. The aim of the study
was to investigate the effect of ingesting a triple-stacked GM corn variety
(NK603 X MON810 X MON863)[2]
on the digestive tract of rats, specifically the stomach mucosa.
Two groups of 10 male Sprague Dawley rats were fed a
diet containing either 60% GM corn (sourced from the United States) or 60%
non-GM corn (sourced from Australia) for 26 weeks. Rats were monitored daily and
weighed weekly including at termination. The stomach was removed immediately
post-mortem and weighed then samples removed and prepared for light microscopy,
immunohistochemistry and electron microscopy.
The authors reported that the GM corn diet had effects
in the rat stomach including alterations to tight junction apposition, gland
dilatations with epithelial elongation and dysplasia. It was suggested that
these effects may have health implications.
FSANZ response
This study was not a guideline study or conducted
according to Good Laboratory Practice (GLP). It contains a number of significant
flaws in study design, conduct and reporting that make it unsuitable for
regulatory purposes, including:
o The source of the rats
was not stated and there was no description of screening for general
health, pathogenic bacteria or viruses.
o
The authors have not stated whether rats were
housed together or individually.
o
Only ten male Sprague Dawley rats were used
for the GM-fed and non-GM groups. This is a
low number of animals for a study of this
type.
o
Although it is claimed that all animal
husbandry was carried out under blinded conditions, it is
unclear how this could have been achieved given
the test diets had to be re-pelleted during the
course of the study.
o
It was not stated whether the animals were
fasted prior to necropsy and the time of necropsy
was not stated.
o
Only one time point was investigated
(terminal necropsy) such that a temporal relationship
could not be established.could not be
established.
o
The control diet did not include an isogenic or near
isogenic corn variety.
o
The method of preparation and storage conditions of the
test diet to prevent mould and insect colonisation
o
Compositional analysis of the two diets (GM; non-GM) was
not conducted and/or reported. Rather, the
nutritional components of a standard rat diet
appear to have been included in the report. If the compositions
of the original GM and non-GM test diets were
comparable to the standard diet, it is unclear why the
reported moisture content of the diets differed
significantly. This should have been addressed by the study
authors.
o
Chemical and microbial contamination of the test diet do
not appear to have been adequately controlled. In
particular the absence of an analytical test for
the presence of mycotoxins was a serious omission because
the GM corn came from the USA, while the non-GM
corn was grown in Australia, and the mycotoxin
contamination could be quite
different.
o
Water consumption does not appear to have been monitored or
reported and may have differed significantly
between GM-fed and non-GM-fed animals,
particularly given the authors suggestion that food consumption
of the two groups was different and less than
anticipated due to low moisture in the test
diets.
Results
No mortality or clinical signs were reported. The
authors reported that food consumption was not as high as expected and that the
GM-fed rats were eating less than non-GM-fed rats. It was suggested that this
may be due to low moisture content in the test diets. However, no data were
provided on body weight, body weight gain, food consumption, water consumption
or even how long it took to reformulate the test diets. Failure to adequately
control or report test diet intake, diet composition, body weight and food and
water consumption are significant flaws in this study.
There was no significant difference in stomach to body
weight ratio. Stomach weight per se was not reported. There was no evidence of
significant treatment-related cellular damage, degeneration or necrosis in the
non-glandular or glandular stomach. Dilated gastric glands are a common
age-related change in rats and not considered to be adverse. The authors state
that the most striking finding was “the loss in tight junction apposition
between mucus-producing cells of the fundus in the GM-fed group”. However this
was also observed in 50% of non-GM fed controls and no historical control data
were provided on background incidence. There was also no evidence that these
changes were related to adverse or functional outcomes.
The study design did not include an investigation of
other endpoints typically required in repeat-dose studies such as haematology,
clinical chemistry, urinalysis, or examination of other organs or tissues at
necropsy that may be used to establish the biological relevance of the observed
findings. Further, it is noted that a range of factors such as nutrients,
hormones, soluble and cellular inflammatory mediators, and bacterial adherence
may all regulate tight junction function and permeability. For example, a
significant omission was the failure to analyse the diet for mycotoxin
contamination. A number of mycotoxins have been shown to alter the gastric
mucosa in rats in a variety of ways, including tight junctions, and in the
absence of a mycotoxin assay of the two diets, the possibility that any subtle
differences in gastric histology are mycotoxin-related and not treatment-related
cannot be eliminated.
FSANZ conclusion
There are a number of serious flaws in the design,
conduct and reporting of this study that make it unsuitable for regulatory
purposes.
[1] Zdziarski,
I.M., Carman, J.A. & Edwards, J.W. (2018). Histopathological investigation
of the stomach of rats fed a 60% genetically modified corn diet. Food and
Nutrition Sciences 9: 763-796.
[2]
Expressing
5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) for glyphosate
tolerance and two Bacillus thuringiensis toxins – Cry1Ab, Cry3Bb1 – for protection against insects.
