**6. Effects on animal health of GM soybean**

In different experiments food and feed derived from GM plants, mixed in animal diets have been fed to rats, mice or other animal species during different periods of administration, and parameters such as body weight, feed consumption, blood chemistry, organ weights, histopathology, etc., have been measured. With respect to recent studies on safety assessment of GM soybeans, the scientific literature shows rather contradictory results.

No immunotoxic activity or an increase in the IgE in serum and histopathological abnormalities were found in the mucosa of the small intestine of rats and mice fed heattreated GM soybean meal containing the cp4-epsps (Teshima et al., 2000).

In Sprague–Dawley rats, Appenzeller et al. (2008) conducted a subchronic feeding study with the herbicide-tolerant soybean DP-356Ø43-5 (356043). Diets were fed to young adult animals for at least 93 days. Compared with rats fed with the isoline control or conventional reference diets, no biologically-relevant, adverse effects were observed in rats fed diets containing 356043 soybean with respect to body weight/gain, food consumption/efficiency, clinical signs, mortality, ophthalmology, neurobehavioral assessments (sensory response, grip strength and motor activity), clinical pathology (hematology, coagulation, serum chemistry and urinalysis), organ weights, and gross and microscopic pathology. Similarly, Delaney et al. (2008) carried out in Sprague–Dawley rats a subchronic feeding study of high oleic acid soybeans (Event DP-3Ø5423-1). DP-3Ø5423-1 (305423) is a GM soybean produced by biolistic insertion of a gm-fad2-1 gene fragment and the gm-hra gene into the germline of soybean seeds. Compared with rats fed the non-GM control diet, no biologically-relevant differences were observed in animals fed the 305423 diet with respect to body weight/gain, food consumption/efficiency, mortality, clinical signs of toxicity, or ophthalmologic observations. In addition, no diet-related effects were noted on neurobehavioral assessment, organ weights, or clinical or anatomic pathology. Based on the results of these studies, the authors concluded that 356043 and 305423 soybeans were as safe and nutritious as conventional non-GM soybeans. Sakamoto et al. (2007; 2008) conducted 52-week and 104 week feeding studies of genetically modified soybeans in F344 rats. Although in both studies several differences in animal growth, food intake, serum biochemical parameters and histological findings were observed between rats fed the GM (glyphosate-tolerant) soybeans and those fed a commercial diet, body weight and food intake were similar for the rats fed the GM and non-GM soybeans. Gross necropsy findings, hematological and serum biochemical parameters, organ weights, and pathological findings showed no meaningful differences between rats fed the GM and non-GM soybeans. These results indicate that longterm intake (54 and 104 weeks) of GM soybeans at the level of 30% in the diet had no apparent adverse effect in rats.

In a 42-day feeding trial study conducted in broiler chickens (McNaughton et al., 2008), it was also concluded that 356043 soybean was nutritionally equivalent to non-transgenic control soybean with a comparable genetic background.

Finally, also related to GM soybeans, Mathesius et al. (2009) assessed the safety of a modified acetolactate synthase protein (GM-HRA) used as a selectable marker in GM

offspring, not in the control group. Those findings show plant DNA fragments are likely to survive digestive processes to some extent (Duggan et al., 2003; Einspanier et al., 2004), as well as their transfer to blood and milk. In addition, the detection of plant DNA in tissues and organs of nursed kids could support the hypothesis of a gene transfer through milk.

In different experiments food and feed derived from GM plants, mixed in animal diets have been fed to rats, mice or other animal species during different periods of administration, and parameters such as body weight, feed consumption, blood chemistry, organ weights, histopathology, etc., have been measured. With respect to recent studies on safety assessment of GM soybeans, the scientific literature shows rather contradictory results. No immunotoxic activity or an increase in the IgE in serum and histopathological abnormalities were found in the mucosa of the small intestine of rats and mice fed heat-

In Sprague–Dawley rats, Appenzeller et al. (2008) conducted a subchronic feeding study with the herbicide-tolerant soybean DP-356Ø43-5 (356043). Diets were fed to young adult animals for at least 93 days. Compared with rats fed with the isoline control or conventional reference diets, no biologically-relevant, adverse effects were observed in rats fed diets containing 356043 soybean with respect to body weight/gain, food consumption/efficiency, clinical signs, mortality, ophthalmology, neurobehavioral assessments (sensory response, grip strength and motor activity), clinical pathology (hematology, coagulation, serum chemistry and urinalysis), organ weights, and gross and microscopic pathology. Similarly, Delaney et al. (2008) carried out in Sprague–Dawley rats a subchronic feeding study of high oleic acid soybeans (Event DP-3Ø5423-1). DP-3Ø5423-1 (305423) is a GM soybean produced by biolistic insertion of a gm-fad2-1 gene fragment and the gm-hra gene into the germline of soybean seeds. Compared with rats fed the non-GM control diet, no biologically-relevant differences were observed in animals fed the 305423 diet with respect to body weight/gain, food consumption/efficiency, mortality, clinical signs of toxicity, or ophthalmologic observations. In addition, no diet-related effects were noted on neurobehavioral assessment, organ weights, or clinical or anatomic pathology. Based on the results of these studies, the authors concluded that 356043 and 305423 soybeans were as safe and nutritious as conventional non-GM soybeans. Sakamoto et al. (2007; 2008) conducted 52-week and 104 week feeding studies of genetically modified soybeans in F344 rats. Although in both studies several differences in animal growth, food intake, serum biochemical parameters and histological findings were observed between rats fed the GM (glyphosate-tolerant) soybeans and those fed a commercial diet, body weight and food intake were similar for the rats fed the GM and non-GM soybeans. Gross necropsy findings, hematological and serum biochemical parameters, organ weights, and pathological findings showed no meaningful differences between rats fed the GM and non-GM soybeans. These results indicate that longterm intake (54 and 104 weeks) of GM soybeans at the level of 30% in the diet had no

In a 42-day feeding trial study conducted in broiler chickens (McNaughton et al., 2008), it was also concluded that 356043 soybean was nutritionally equivalent to non-transgenic

Finally, also related to GM soybeans, Mathesius et al. (2009) assessed the safety of a modified acetolactate synthase protein (GM-HRA) used as a selectable marker in GM

treated GM soybean meal containing the cp4-epsps (Teshima et al., 2000).

**6. Effects on animal health of GM soybean** 

apparent adverse effect in rats.

control soybean with a comparable genetic background.

soybeans. The authors did not find adverse effects in mice following acute oral exposure to GM-HRA at a dose of at least 436 mg/kg of body weight, or in a 28-day repeated dose dietary toxicity study at doses up to 1247 mg/kg of body weight/day. It was concluded that GM-HRA protein is safe when used in agricultural biotechnology.

In contrast to the above results, in a long-term study on female mice fed with a GM modified soybean (insertion of the bacterial CP4 EPSPS gene to confer a high level of tolerance to glyphosate), focused on assessing the effects of this diet on liver of old animals (until 24 months of age) and to elucidate possible interference with aging, Malatesta et al. (2008a) found that GM soybean intake could influence the liver morpho-functional features during the physiological process of aging. Several proteins belonging to hepatocyte metabolism, stress response, calcium signaling and mitochondria were differentially expressed in GM-fed mice, indicating a more marked expression of senescence markers in comparison to controls. Moreover, hepatocytes of GM-fed mice showed mitochondrial and nuclear modifications indicative of reduced metabolic rate. In previous studies on hepatocytes from young and adult (2–8 months of age) female mice fed GM soybeans, nuclear modifications involving structural constituents of the transcription and splicing properties pathways were seen (Malatesta et al., 2002a). Although the cause(s) of the observed alterations could not be conclusively established, it was noted that these modifications disappeared when GM soybean was replaced by a non-GM one in the diet (Malatesta et al., 2005). Since the GM soybean used was tolerant to glyphosate and was treated with the glyphosate-containing herbicide Roundup, the effects observed might be due to herbicide residues. Accordingly, and aiming to verify this hypothesis, Malatesta et al. (2008b) treated rat hepatoma tissue culture (HTC) cells with 1–10 mM Roundup and analyzed cellular features by flow cytometry, fluorescence, and electron microscopy. Under these experimental conditions, the death rate and the general morphology of HTC cells were not affected, as well as most of the cytoplasmic organelles. However, in HTC-treated cells, lysosome density increased and mitochondrial membranes were modified indicating a decline in the respiratory activity. In addition to the above, nuclei underwent morphofunctional modifications suggesting a decreased transcriptional/splicing activity. The authors did not exclude that factors other than the presence of the herbicide residues could be responsible for the cellular modifications described in GM-fed mice. However, they indicated that the concordance of the effects induced by low concentrations of Roundup on HTC cells suggested that the presence of Roundup residues could be one of the factors interfering with multiple metabolic pathways.

Cisterna et al. (2008) investigated the ultrastructural and immunocytochemical features of pre-implantation embryos from mice fed either GM or non-GM soybean in order to verify whether the parental diet could affect the morpho-functional development of the embryonic ribonucleoprotein structural constituents involved in pre-mRNA pathways. Morphological observations revealed that the general aspect of embryo nuclear components were similar in the GM and non-GM soybean-exposed groups. However, immunocytochemical and in situ hybridization results suggested a temporary decrease of pre-mRNA transcription and splicing in 2-cell embryos and a resumption in 4–8-cell embryos from mice fed GM soybean. In addition, pre-mRNA maturation seemed to be less efficient in both 2-cell and 4–8-cell embryos from GM-fed mice than in non-GM-fed animals.

Battistelli et al. (2010) investigated the duodenum and colon of mice fed on genetically modified (GM) soybean during their whole life span (1-24 months) by focusing their attention on the histological and ultrastructural characteristics of the epithelium, the

Genetically Modified Soybean in Animal Nutrition 143

two weeks before mating, during the pregnancy and during suckling and the body mass and the number of pups were observed. The data indicated that on the GM soybeansupplemented rat chow significantly fewer pups were born, and with smaller body mass,

In order to evaluate the possible health effects of a GM diet, Tudisco et al (2006) studied the activity of organ specific enzymes in two groups of New Zealand rabbits, given a diet

Statistical differences were detected in kidney for alanine aminotransferase (ALT), gamma glutamyltransferase (GGT) and lactic dehydrogenase (LDH) (higher activity for group fed GM soybean) whereas in the heart such result was seen only for LDH. No statistical differences were found for serum, liver and skeletal muscle. Significant differences between groups were detected for heart LDH1 and LDH2 and for kidney LDH1, thus confirming the significant increase of the enzyme in these tissues. Moreover, despite no significant differences were found for LDH total activity in liver, a significant increase (LDH1) and

Brasil et al. (2009) found that rats fed on GM soy showed altered morphology of the uterus and the ovaries: had greater volume density of endometrial glanular epithelium, reduced follicle number and increased corpus luteum numbers (a tendency to abort or less of a chance to get pregnant). Although the GM diet was not supplemented with cysteine as the other diets, and it is difficult to assess if the results were due to consumption of the transgenic soy itself or were due to the presence of glyphosate (and/or AMPA), always

A recent study found that the hamsters fed with GM Soybean showed the growth of hairs inside the pouches of the mouth and the number of hairy mouthed hamsters was much higher in the third generation of GM soy fed animals than in others (Baranov et al., 2010). According to the authors, it remains unclear why these hair structures appear in the oral cavity of mammals. We may only speculate on the origin of this phenomenon. The gingival pouches may result from paradontitis and paradontosis caused by feeding on compound food in the vivarium, i.e., by a suboptimal diet. This pathology may be exacerbated by elements of the food that are absent in natural food, such as genetically modified (GM) ingredients (GM soybean or corn meal) or contaminants (pesticides, mycotoxins, heavy metals, etc.). Probably, hair growth in the gingival pouches is a protective reaction of the body suppressing the progress of gingival pathology, because the hair bundles are so dense that they prevent food from getting into the pouches and the resultant inevitable inflammation. Hair grows in the parts of the mucosa that, being affected by mechanical

More recently, Tudisco et al (2010) studied the possible effects on cell metabolism, by determination of several specific enzymes in serum of goats fed conventional or Roundup Ready soybean and in heart, skeletal muscle, liver and kidney of their offspring. Aspartate aminotransferase (AST) and ALT enzyme activity were significantly lower in serum from goats fed GM soybean but enzyme levels were in the normal range. Statistical differences were detected in kid's kidney for GGT and LDH, whereas in the heart and skeletal muscle this result was seen only for LDH. The increase in LDH activity was confirmed by histochemistry. In addition, significant differences between control and treated animals were detected for heart, kidney, muscles and liver LDH isoenzyme distribution, particularly concerning the LDH1, as found previously in the rabbits. Since LDH1 is known to be involved in cell metabolism by favouring the reaction of lactate to pyruvate (Van Hall, 2000),

containing soybean meal which was from conventional or Roundup Ready beans.

present in GM seeds, the findings are disturbing and warrant further studies.

than on the control non-GM soybeans.

decrease (LDH4) were found also in this organ.

factors, acquire the capacity for keratinization.

these results could indicate a general increase in cell metabolism.

histochemical pattern of goblet cell mucins, and the growth profile of the coliform population. Even if the GM soybean-containing diet did not induce structural alterations in duodenal and colonic epithelium or in coliform population, the histochemical approach revealed significant diet-related changes in mucin amounts in the duodenum. In particular, the percentage of villous area occupied by acidic and sulphomucin granules decreased from controls to GM-fed animals.

In a previous ultrastructural analysis of testes from mice fed GM soybean conducted by the same research group (Vecchio et al., 2004), it was found that the immunolabelling for Sm antigen, hnRNPs, SC35 and RNA Polymerase II was decreased in 2 and 5 month-old GMfed mice, and was restored to normal at 8 months. In GM-fed mice of all ages considered, the number of perichromatin granules was higher and the nuclear pore density lower. Moreover, enlargements in the smooth endoplasmic reticulum in GM-fed mice Sertoli cells were also observed. Consequently, all these studies at the microscopic and ultramicroscopic levels showed cellular changes attributable to GM soybean intake.

Magaña-Gómez et al. (2008) conducted a study in Wistar rats, in which the hypothesis was that the intake of GM (SUPRO 500E) soybean could induce pancreatic stress or injury by analyzing the expression of pancreatitis-associated protein (PAP) and trypsinogens by qRT-PCR in rats fed GM soy protein for 30 days. The hypothesis was based on the results of previous investigations showing that mice chronically fed since gestation with GM had problems in synthesis and processing of zymogens by pancreatic acinar cells and reduced nucleoplasmic and nucleolar and perichromatin granule accumulation on pancreatic acinar cell nuclei (Malatesta et al., 2002b; 2003). Magaña-Gómez et al. (2008) did not find differences in nutritional performance among rats fed non-GM and GM diets. The GM diet induced significant zymogen-granule depletion after 15 days feeding, returning to normal levels after 30 days. Acinar disorganization started as early as 5 days after initiation of the GM diet and it recovered after 30 days. Levels of PAP mRNA significantly increased in the GM diet between day 1 and day 3 and decreased to the basal level by day 15. In turn, trypsinogen mRNA peaked at two different times: at day 1 and at day 15, decreasing to basal levels after 30 days, while plasma amylase levels remained unchanged at all times. The authors indicated that GM soy protein intake affected pancreas function, evidenced by the early acute PAP mRNA increased levels and pancreas cellular changes followed by recuperation of acinar cells after 30 days.

Evaluating the GM soybean in Atlantic salmon diet, enlarged spleen and possible impaired spleen function as the number of smaller-sized red blood cells simultaneously increased were indicated (Hemre et al., 2005).

The same authors (Sagstad et al., 2008) reported lower plasma triacylglycerol levels and a significantly larger spleen somatic index in fish groups fed GM soybean compared to groups fed non-GM soybean.

Ermakova ( 2006) examined the effect of glyphosate-resistant (RR) GM soybean seeds fed to pregnant female rats on the number and weight of pups delivered The study was originally published in Russian, and was heavily criticised for using coated seeds ready for planting instead of beans suitable for feed. The control non-GM soybean was not the isogenic parent line, either. However, because of the possible serious implications of the results of this study for humans and animals it should have been repeated and possibly verified by other scientists with the correct GM soybean diets. Indeed, she has repeatedly pleaded for this but no one dared to try to reproduce her experiments. In this study rats were fed with laboratory rat chow and this diet was complemented with GM or conventional soybean for

histochemical pattern of goblet cell mucins, and the growth profile of the coliform population. Even if the GM soybean-containing diet did not induce structural alterations in duodenal and colonic epithelium or in coliform population, the histochemical approach revealed significant diet-related changes in mucin amounts in the duodenum. In particular, the percentage of villous area occupied by acidic and sulphomucin granules decreased from

In a previous ultrastructural analysis of testes from mice fed GM soybean conducted by the same research group (Vecchio et al., 2004), it was found that the immunolabelling for Sm antigen, hnRNPs, SC35 and RNA Polymerase II was decreased in 2 and 5 month-old GMfed mice, and was restored to normal at 8 months. In GM-fed mice of all ages considered, the number of perichromatin granules was higher and the nuclear pore density lower. Moreover, enlargements in the smooth endoplasmic reticulum in GM-fed mice Sertoli cells were also observed. Consequently, all these studies at the microscopic and ultramicroscopic

Magaña-Gómez et al. (2008) conducted a study in Wistar rats, in which the hypothesis was that the intake of GM (SUPRO 500E) soybean could induce pancreatic stress or injury by analyzing the expression of pancreatitis-associated protein (PAP) and trypsinogens by qRT-PCR in rats fed GM soy protein for 30 days. The hypothesis was based on the results of previous investigations showing that mice chronically fed since gestation with GM had problems in synthesis and processing of zymogens by pancreatic acinar cells and reduced nucleoplasmic and nucleolar and perichromatin granule accumulation on pancreatic acinar cell nuclei (Malatesta et al., 2002b; 2003). Magaña-Gómez et al. (2008) did not find differences in nutritional performance among rats fed non-GM and GM diets. The GM diet induced significant zymogen-granule depletion after 15 days feeding, returning to normal levels after 30 days. Acinar disorganization started as early as 5 days after initiation of the GM diet and it recovered after 30 days. Levels of PAP mRNA significantly increased in the GM diet between day 1 and day 3 and decreased to the basal level by day 15. In turn, trypsinogen mRNA peaked at two different times: at day 1 and at day 15, decreasing to basal levels after 30 days, while plasma amylase levels remained unchanged at all times. The authors indicated that GM soy protein intake affected pancreas function, evidenced by the early acute PAP mRNA increased levels and pancreas cellular changes followed by

Evaluating the GM soybean in Atlantic salmon diet, enlarged spleen and possible impaired spleen function as the number of smaller-sized red blood cells simultaneously increased

The same authors (Sagstad et al., 2008) reported lower plasma triacylglycerol levels and a significantly larger spleen somatic index in fish groups fed GM soybean compared to groups

Ermakova ( 2006) examined the effect of glyphosate-resistant (RR) GM soybean seeds fed to pregnant female rats on the number and weight of pups delivered The study was originally published in Russian, and was heavily criticised for using coated seeds ready for planting instead of beans suitable for feed. The control non-GM soybean was not the isogenic parent line, either. However, because of the possible serious implications of the results of this study for humans and animals it should have been repeated and possibly verified by other scientists with the correct GM soybean diets. Indeed, she has repeatedly pleaded for this but no one dared to try to reproduce her experiments. In this study rats were fed with laboratory rat chow and this diet was complemented with GM or conventional soybean for

levels showed cellular changes attributable to GM soybean intake.

controls to GM-fed animals.

recuperation of acinar cells after 30 days.

were indicated (Hemre et al., 2005).

fed non-GM soybean.

two weeks before mating, during the pregnancy and during suckling and the body mass and the number of pups were observed. The data indicated that on the GM soybeansupplemented rat chow significantly fewer pups were born, and with smaller body mass, than on the control non-GM soybeans.

In order to evaluate the possible health effects of a GM diet, Tudisco et al (2006) studied the activity of organ specific enzymes in two groups of New Zealand rabbits, given a diet containing soybean meal which was from conventional or Roundup Ready beans.

Statistical differences were detected in kidney for alanine aminotransferase (ALT), gamma glutamyltransferase (GGT) and lactic dehydrogenase (LDH) (higher activity for group fed GM soybean) whereas in the heart such result was seen only for LDH. No statistical differences were found for serum, liver and skeletal muscle. Significant differences between groups were detected for heart LDH1 and LDH2 and for kidney LDH1, thus confirming the significant increase of the enzyme in these tissues. Moreover, despite no significant differences were found for LDH total activity in liver, a significant increase (LDH1) and decrease (LDH4) were found also in this organ.

Brasil et al. (2009) found that rats fed on GM soy showed altered morphology of the uterus and the ovaries: had greater volume density of endometrial glanular epithelium, reduced follicle number and increased corpus luteum numbers (a tendency to abort or less of a chance to get pregnant). Although the GM diet was not supplemented with cysteine as the other diets, and it is difficult to assess if the results were due to consumption of the transgenic soy itself or were due to the presence of glyphosate (and/or AMPA), always present in GM seeds, the findings are disturbing and warrant further studies.

A recent study found that the hamsters fed with GM Soybean showed the growth of hairs inside the pouches of the mouth and the number of hairy mouthed hamsters was much higher in the third generation of GM soy fed animals than in others (Baranov et al., 2010). According to the authors, it remains unclear why these hair structures appear in the oral cavity of mammals. We may only speculate on the origin of this phenomenon. The gingival pouches may result from paradontitis and paradontosis caused by feeding on compound food in the vivarium, i.e., by a suboptimal diet. This pathology may be exacerbated by elements of the food that are absent in natural food, such as genetically modified (GM)

ingredients (GM soybean or corn meal) or contaminants (pesticides, mycotoxins, heavy metals, etc.). Probably, hair growth in the gingival pouches is a protective reaction of the body suppressing the progress of gingival pathology, because the hair bundles are so dense that they prevent food from getting into the pouches and the resultant inevitable inflammation. Hair grows in the parts of the mucosa that, being affected by mechanical factors, acquire the capacity for keratinization.

More recently, Tudisco et al (2010) studied the possible effects on cell metabolism, by determination of several specific enzymes in serum of goats fed conventional or Roundup Ready soybean and in heart, skeletal muscle, liver and kidney of their offspring. Aspartate aminotransferase (AST) and ALT enzyme activity were significantly lower in serum from goats fed GM soybean but enzyme levels were in the normal range. Statistical differences were detected in kid's kidney for GGT and LDH, whereas in the heart and skeletal muscle this result was seen only for LDH. The increase in LDH activity was confirmed by histochemistry. In addition, significant differences between control and treated animals were detected for heart, kidney, muscles and liver LDH isoenzyme distribution, particularly concerning the LDH1, as found previously in the rabbits. Since LDH1 is known to be involved in cell metabolism by favouring the reaction of lactate to pyruvate (Van Hall, 2000), these results could indicate a general increase in cell metabolism.

Genetically Modified Soybean in Animal Nutrition 145

Wistar rats 30 days Significant zymogen-granule depletion

Table 4. A summary of experimental studies concerning health of animals fed with

Glyphosate is not a genetically modified product but because its use in agriculture is inseparable from the cultivation of herbicide-tolerant GM crops in a particular technology package, its effects on health need to be examined also with that of the glyphosate-resistant GM crops. Although the declared aim of the introduction of glyphosate resistant GM crops was that with these crops the amount of herbicide sprayed on the land should decrease, due to the ever increasing area of cultivation of glyphosate-resistant Roundup Ready GM crops, the use of glyphosate has in fact increased (Benbrook, 2004; 2009). The glyphosatecontaining sprays destroy all weeds but the growth of the glyphosate-resistant GM crop is protected regardless of how much glyphosate is sprayed on to the land. To make sure that all weeds are destroyed the use of glyphosate and consequently the glyphosate load of the land has been substantially increasing after the first few years of a slight reduction (Benbrook, 2004; 2009). This has happened despite the ever-increasing number of publications showing that glyphosate has many serious and detrimental effects on the environment and biodiversity (Relyea 2005) with the development of herbicide-resistant weeds (Duke, 2005; Owen & Zelaya 2005; Warwick et al., 2008; Zelaya et al., 2007). There is also an urgent need to consider the potentially seriously damaging effects of this total

Pregnant Rats 2 weeks Fewer pups born with smaller body

No morphological differences in embryos of GM and non-Gm soybeanexposed groups. Microscopic and ultramicroscopic cellular changes attributed to GM soybean intake

No adverse effects in nutritional performance. Altered pancreas function evidenced by the early acute PAP mRNA increased levels and pancreas cellular changes

mass

Significant alteration of kidney ALT, GGT and LDH activity. Significant alteration of heart LDH activity

Growth of hairs inside the pouches of the mouth and the number of hairy mouthed

Significant alteration of kidney GGT and LDH activity. Significant alteration of LDH isoenzyme distribution in heart, kidney, muscle and liver

Cisterna et al. (2008)

(Malatesta et al., 2002a) and (Malatesta et al., 2002b)

Magaña-Gómez et al. (2008)

Ermakova et al. (2006)

Tudisco et al. (2006)

Baranov et al. (2010)

Tudisco et al. (2010)

Mice –

Wistar rats 30 days

Rabbits 60 days

Kids 60 days

genetically modified soybean.

**7. Human/animal safety of glyphosate** 

Hamsters -

A summary of experimental studies concerning health of animals fed genetically modified soybean is reported in Table 4.


A summary of experimental studies concerning health of animals fed genetically modified

**study Main effects Reference** 

Teshima et al. (2000)

Appenzeller et al. (2008)

Delaney et al. (2008)

al. (2009)

Sakamoto et al. (2007)

Sakamoto et al. (2008)

McNaughton et al. (2008)

Vecchio et al. (2004)

Malatesta et al. (2008a)

histopathological abnormalities.

No adverse effects on body weight/gain, food consumption, clinical signs, mortality, ophthalmology, neurobehavioral assessment, clinical pathology, organ weights and gross and microscopic pathology

No adverse effects on body weight/gain, food consumption, and mortality, clinical signs of toxicity or ophthalmological observations, neurobehavioral assessments, organ weights or clinical and anatomic pathology

No adverse effect in gross necropsy findings, hematological and serum biochemical parameters, organ weights and pathological findings

No adverse effect in gross necropsy findings, hematological and serum biochemical parameters, organ weights and pathological findings

No adverse effects were found. It was concluded that GM 356Ø43 was nutritionally equivalent to non-GM soybean with comparable genetic background

endoplasmic reticulum of Sertoli cells

Several proteins belonging to hepatocyte metabolism, stress response, calcium signaling and mitochondria were differentially expressed in GM-fed mice indicating a more marked expression of senescence markers in comparison to controls. GM-fed mice showed mitochondrial and nuclear modifications indicative of reduced metabolic rate

Mice 28 days No adverse effects Mathesius et

soybean is reported in Table 4.

Dawley rats > 93 days

Dawley rats –

F344 rats 52 weeks

F344 rats 104 weeks

Broilers 42 days

Mice –

**Length of** 

B10A mice 15 weeks No immunotoxic activity. No

Mice - Enlargements in the smooth

**Animal species** 

BN rats and

Sprague–

Sprague–


Table 4. A summary of experimental studies concerning health of animals fed with genetically modified soybean.
