Citation: Kilic, A. and M. T. Akay (2008).
A three generation study with genetically modified Bt corn in rats: Biochemical and histopathological investigation.
Food Chem. Toxicol. 46(3): 1164-1170.
For the last ten years, in accordance with the increased use of genetically modified (GM) foods for human and livestocks, a large number of feeding studies have been carried out. However, the evidence is still far from proving whether the long-term consumption of GM foods posses a possible danger for human or animal health. Therefore, this study was designed to evaluate the effects of transgenic corn on the rats that were fed through three generations with either GM corn or its conventional counterpart. Tissue samples of stomach, duodenum, liver and kidney were obtained for histopathological examinations. The average diameter of glomeruli, thickness of renal cortex and glomerular volume were calculated and number of affected animals/number of examined animals for liver and kidney histopathology were determined. Amounts of urea, urea nitrogen, creatinine, uric acid, total protein, albumin and globulin were determined; enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyltransferase, creatine kinase and amylase were measured in serum samples. No statistically significant differences were found in relative organ weights of rats within groups but there were some minimal histopathological changes in liver and kidney. Changes in creatinine, total protein and globulin levels were also determined in biochemical analysis.
Preliminary impressions from another worker in this field:
* This paper claims that the feeding programme resulted in no untoward effects on the animals fed with GM maize MON810. However, the quality of the research leaves much to be desired, and it is surprising that it got through the peer review process. The researchers presumably obtained samples of the Bt corn and the non- GM corn from the Turkish Government's own Agriculture Dept. No description is made of the non-GM variety, including its name. Monsanto has in the past, used varieties that have gone through the GM process but not taken up the transgene, as 'controls". No real mention is made of the fact that the GM corn must be MON810 corn and absolutely no mention is made of the fact that it is made by Monsanto. Why not? Researchers have to sign all sorts of agreements with Monsanto to get anywhere near being able to be given samples of GM grain, so we may assume that the researchers expected to find no difference between the GM and non-GM grain and were embarrassed when they did. Specific defects in the research: * They used fairly old rats, not just post-weaned, so the animals were less likely to show adverse effects. * They used corn at only 20% of the diet. Even Monsanto has used 33%. They have two control groups and many of the analyses are actually between the two control groups. * They have used SE as a measure of variance instead of SD. This tends to reduce the apparent variance and makes the data look tighter than it is. * They have small sample sizes - blood biochemistry by gender is only n=5, so it is hard to find statistical significance. Of course, they found little statistical significance there! * Of real concern to me are the results in table 4. It indicates that there is something very weird happening in one or both of the control groups. The liver weight of group I is 16.4% of the body weight of the rats while the liver weight in Group II (the 20% corn control group) is only 2.7% of the body weight. Either the livers in group I are swollen or the livers in group II have shrunk shockingly. * In table 3, the group I control has less F3 offspring. I didn't think that feeding corn (whether GM or not) increased the number of offspring compared to feeding ordinary rat chow! * They clearly have found problems in the liver and kidneys of animals fed the GM corn (Table 5) * They have concluded, despite the evidence that feeding the GM corn did cause harm, that it "did not cause severe health concerns on rats". That is a matter of opinion.......? * No mention is made of where funding for the research came from.
Comment from another peer reviewer:
The Turkish paper appears to me to have been remarkably badly conducted. Apart from the almost unreadable English, I'd point out:
1. This information appears to have been drawn entirely from 6 females per treatment, and their subsequent offspring. There is no replication in time - the trial was not repeated with a different starting group of females.
2. We are not told the range in starting weight of the starting group of 18 females. Because large magnitude arithmetic differences in subsequent performance are not found to be statistically different, one may wonder at the possible heterogeneity in weight of the starting females. This is one of several key omissions. Likewise, F3 rats were sacrified at 3.5 months of age - why this age, and would results have differed from earlier, later, or sequential sampling?
3. The comparability of the 3 diets is quite unclear. We are told nothing about the Standard diet - does it contain any corn at all? This becomes important when comparing performance on the 3 diets and the Group I animals appear to be responding v. differently from II and III, which are more similar. We are given composition of the experimental diets (Table 1) but not the Standard - why?
4. There does not appear to have been any effort to standardize the 3 diets in terms of energy or protein, or to statistically compare the composition of the Bt and non-Bt corn. Table 1 is labelled 'composition of experimental diets', but it appears to have been composition of the corn part of the diet only. If the diets are not themselves standardized then, this introduces a source of ambiguity into interpretation of differences, or lack of differences.
5. Animals received set amounts of feed - not free choice. Is there a reason for this? Does limited feed hinder expression of palatability or other differences among rations?
6. I'm unclear on the mating design. Presumably, the original females were not bred repeatedly, but their offspring were bred to contribute the F2, and then their offspring to make the F3?
7. The number of animals in the F2 and F3 generations appear to differ substantially among trts, particularly in the F2 and F3 generations, and particularly between the Standard and corn-based rations (50% more individuals than on the standard ration). What does it mean that different numbers of individuals made it into the F2 and F3 - depending on the ration - and why were all of them analyzed for body weight etc. rather than just 6 per generation? In Table 4, groups varying in size from 5 to 14 females and from 14 to 22 males were compared statistically, they claim to have tested for homogeneity of variance but this seems implausible, given numerous anomalous results. For example, female liver weights where 6.7 does not differ from 25.1, but both of them differ from 33? Likewise Table 5 where arithmetically large differences are ns. For females in particular, all parameters shown in Table 5 appear to distinguish III from either I or II - but the interpretation ("damages were minor but not critical to animal health") minimizes the meaning of these differences - or gender specific differences. Comparing grossly unequal sample sizes appears to have contributed to the finding of no significant difference.
8. Fig 1 doesn't indicate if it is male or female animals, or which generation - but presumably F3 as this was the only one subjected to examination?
9. Why limit the corn to 20%? Are rats not meant to eat corn? What is the safety margin of 33% corn?